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ALLERGOLOGY AND IMMUNOLOGY (212 journals)                  1 2 | Last

Showing 1 - 200 of 212 Journals sorted alphabetically
Acta Microbiologica et Immunologica Hungarica     Full-text available via subscription   (Followers: 4)
Advances in Immunology     Full-text available via subscription   (Followers: 37)
AIDS Research and Therapy     Open Access   (Followers: 14)
Alergologia Polska : Polish Journal of Allergology     Full-text available via subscription   (Followers: 1)
Allergies     Open Access   (Followers: 1)
Allergo Journal     Full-text available via subscription   (Followers: 1)
Allergo Journal International     Hybrid Journal   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1)
Allergology International     Open Access   (Followers: 5)
Allergy     Hybrid Journal   (Followers: 50)
Allergy & Rhinology     Open Access   (Followers: 4)
Allergy and Asthma Proceedings     Full-text available via subscription   (Followers: 14)
Allergy, Asthma and Clinical Immunology     Open Access   (Followers: 26)
American Journal of Epidemiology     Hybrid Journal   (Followers: 216)
American Journal of Immunology     Open Access   (Followers: 23)
American Journal of Preventive Medicine     Hybrid Journal   (Followers: 29)
American Journal of Reproductive Immunology     Hybrid Journal   (Followers: 6)
American Journal of Rhinology and Allergy     Hybrid Journal   (Followers: 9)
Annals of Allergy, Asthma and Immunology     Hybrid Journal   (Followers: 14)
Annals of Allergy, Asthma, and Immunology     Hybrid Journal  
Annual Review of Immunology     Full-text available via subscription   (Followers: 50)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 5)
Applied Immunohistochemistry & Molecular Morphology     Hybrid Journal   (Followers: 16)
Archives of Asthma, Allergy and Immunology     Open Access  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2)
Autoimmune Diseases     Open Access   (Followers: 3)
Autoimmunity     Hybrid Journal   (Followers: 9)
Autoimmunity Highlights     Open Access   (Followers: 2)
Autoimmunity Reviews     Hybrid Journal   (Followers: 3)
BMC Immunology     Open Access   (Followers: 11)
Cancer Immunology, Immunotherapy     Hybrid Journal   (Followers: 22)
Case Reports in Immunology     Open Access   (Followers: 6)
Cellular & Molecular Immunology     Hybrid Journal   (Followers: 15)
Cellular Immunology     Hybrid Journal   (Followers: 31)
Chronic Diseases and Injuries in Canada     Free   (Followers: 1)
Clinica Chimica Acta     Hybrid Journal   (Followers: 28)
Clinical & Experimental Allergy     Hybrid Journal   (Followers: 7)
Clinical & Experimental Allergy Reviews     Hybrid Journal   (Followers: 1)
Clinical & Experimental Immunology     Hybrid Journal   (Followers: 18)
Clinical & Translational Immunology     Open Access   (Followers: 8)
Clinical and Experimental Neuroimmunology     Hybrid Journal   (Followers: 1)
Clinical and Molecular Allergy     Open Access   (Followers: 5)
Clinical and Translational Allergy     Open Access   (Followers: 2)
Clinical Immunology     Hybrid Journal   (Followers: 25)
Clinical Immunology, Endocrine & Metabolic Drugs     Hybrid Journal  
Clinical Reviews in Allergy and Immunology     Hybrid Journal   (Followers: 12)
Comparative Immunology, Microbiology and Infectious Diseases     Hybrid Journal   (Followers: 14)
Critical Reviews in Immunology     Full-text available via subscription   (Followers: 15)
Current Allergy & Clinical Immunology     Open Access   (Followers: 8)
Current Allergy and Asthma Reports     Hybrid Journal   (Followers: 2)
Current Immunology Reviews     Hybrid Journal   (Followers: 10)
Current Opinion in Allergy and Clinical Immunology     Hybrid Journal   (Followers: 8)
Current Opinion in Immunology     Hybrid Journal   (Followers: 44)
Current Opinion in Virology     Hybrid Journal   (Followers: 1)
Current Protocols in Immunology     Hybrid Journal  
Current Treatment Options in Allergy     Hybrid Journal   (Followers: 2)
Developmental & Comparative Immunology     Hybrid Journal   (Followers: 7)
Egyptian Journal of Pediatric Allergy and Immunology     Open Access   (Followers: 2)
Emerging Infectious Diseases     Open Access   (Followers: 30)
Epidemiologic Methods     Hybrid Journal   (Followers: 4)
European Annals of Allergy and Clinical Immunology     Open Access   (Followers: 5)
European Journal of Immunology     Hybrid Journal   (Followers: 39)
European Journal of Microbiology and Immunology     Open Access   (Followers: 11)
Expert Review of Clinical Immunology     Full-text available via subscription   (Followers: 5)
Expert Review of Vaccines     Full-text available via subscription   (Followers: 4)
Food and Agricultural Immunology     Open Access   (Followers: 2)
Frontiers in Immunology     Open Access   (Followers: 20)
Future Virology     Hybrid Journal   (Followers: 8)
Genes & Immunity     Hybrid Journal   (Followers: 8)
Handbook of Systemic Autoimmune Diseases     Full-text available via subscription   (Followers: 2)
HLA Immune Response Genetics     Hybrid Journal  
HNO Nachrichten     Full-text available via subscription  
Human Immunology     Hybrid Journal   (Followers: 18)
Human Vaccines & Immunotherapeutics     Full-text available via subscription   (Followers: 2)
Hypersensitivity     Open Access   (Followers: 1)
Immunity     Full-text available via subscription   (Followers: 65)
Immunity & Ageing     Open Access   (Followers: 10)
Immunity, Inflammation and Disease     Open Access   (Followers: 6)
Immuno-analyse & Biologie Spécialisée     Full-text available via subscription   (Followers: 2)
Immunobiology     Hybrid Journal   (Followers: 9)
Immunoendocrinology     Open Access   (Followers: 1)
Immunogenetics     Hybrid Journal   (Followers: 6)
ImmunoHorizons     Open Access  
Immunologic Research     Hybrid Journal   (Followers: 6)
Immunological Investigations: A Journal of Molecular and Cellular Immunology     Hybrid Journal   (Followers: 2)
Immunological Medicine     Open Access  
Immunological Reviews     Hybrid Journal   (Followers: 27)
Immunology     Hybrid Journal   (Followers: 38)
Immunology & Cell Biology     Hybrid Journal   (Followers: 9)
Immunology and Allergy Clinics of North America     Full-text available via subscription   (Followers: 6)
Immunology and Immunogenetic Insights     Open Access   (Followers: 5)
Immunology and Infectious Diseases     Open Access   (Followers: 9)
Immunology Innovation     Open Access   (Followers: 2)
Immunology Letters     Hybrid Journal   (Followers: 13)
Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry     Hybrid Journal   (Followers: 3)
Immunome Research     Open Access   (Followers: 6)
ImmunoTargets and Therapy     Open Access   (Followers: 2)
Immunotherapy     Hybrid Journal   (Followers: 7)
Immunotoxicology of Drugs and Chemicals: an Experimental and Clinical Approach     Full-text available via subscription   (Followers: 1)
Indian Journal of Allergy, Asthma and Immunology     Open Access   (Followers: 1)
Infectious Diseases: Research and Treatment     Open Access   (Followers: 4)
Inflammation & Allergy - Drug Targets     Hybrid Journal   (Followers: 2)
Inmunología     Full-text available via subscription   (Followers: 2)
Innate Immunity     Hybrid Journal   (Followers: 7)
International Archives of Allergy and Immunology     Full-text available via subscription   (Followers: 1)
International Forum of Allergy & Rhinology     Hybrid Journal   (Followers: 4)
International Immunology     Hybrid Journal   (Followers: 3)
International Immunopharmacology     Hybrid Journal   (Followers: 2)
International Journal of Immunological Studies     Hybrid Journal   (Followers: 1)
International Journal of Immunopathology and Pharmacology     Full-text available via subscription   (Followers: 2)
International Journal of Infectious Diseases     Open Access   (Followers: 9)
International Journal of Virology     Open Access   (Followers: 2)
International Reviews Of Immunology     Hybrid Journal   (Followers: 4)
Internet Journal of Rheumatology and Clinical Immunology     Open Access   (Followers: 5)
Iranian Journal of Allergy, Asthma and Immunology     Open Access  
Joint Commission Journal on Quality and Patient Safety     Hybrid Journal   (Followers: 40)
Journal des Anti-infectieux     Full-text available via subscription   (Followers: 2)
Journal of Allergy & Therapy     Open Access   (Followers: 2)
Journal of Clinical & Cellular Immunology     Open Access   (Followers: 3)
Journal of Vaccines & Vaccination     Open Access   (Followers: 4)
Journal of Allergy and Clinical Immunology     Hybrid Journal   (Followers: 31)
Journal of Allergy and Clinical Immunology : In Practice     Full-text available via subscription   (Followers: 13)
Journal of Asthma Allergy Educators     Hybrid Journal   (Followers: 4)
Journal of Asthma and Allergy     Open Access   (Followers: 8)
Journal of Autoimmunity     Hybrid Journal   (Followers: 15)
Journal of Cellular Immunotherapy     Open Access   (Followers: 4)
Journal of Clinical Immunology     Hybrid Journal   (Followers: 14)
Journal of Clinical Immunology and Immunopathology Research     Open Access   (Followers: 5)
Journal of General Virology     Full-text available via subscription   (Followers: 11)
Journal of Immune Based Therapies, Vaccines and Antimicrobials     Open Access   (Followers: 2)
Journal of Immunological Methods     Hybrid Journal   (Followers: 46)
Journal of Immunological Techniques in Infectious Diseases     Hybrid Journal   (Followers: 3)
Journal of Immunology     Full-text available via subscription   (Followers: 68)
Journal of Immunology and Clinical Microbiology     Open Access   (Followers: 2)
Journal of Immunology and Regenerative Medicine     Hybrid Journal   (Followers: 1)
Journal of Immunology Research     Open Access   (Followers: 9)
Journal of Immunotherapy     Hybrid Journal   (Followers: 7)
Journal of Immunotherapy Applications     Open Access  
Journal of Immunotoxicology     Open Access   (Followers: 3)
Journal of Infection Prevention     Hybrid Journal   (Followers: 16)
Journal of Infectious Diseases and Immunity     Open Access   (Followers: 8)
Journal of Innate Immunity     Open Access   (Followers: 6)
Journal of Medical Genetics and Genomics     Open Access   (Followers: 3)
Journal of Microbiology, Immunology and Infection     Open Access   (Followers: 9)
Journal of Neuroimmunology     Hybrid Journal   (Followers: 6)
Journal of NeuroVirology     Hybrid Journal   (Followers: 1)
Journal of Reproductive Immunology     Hybrid Journal   (Followers: 2)
Journal of the Pediatric Infectious Diseases Society     Hybrid Journal   (Followers: 11)
Journal of Translational Autoimmunity     Open Access  
Medical Immunology     Open Access   (Followers: 20)
Medical Microbiology and Immunology     Hybrid Journal   (Followers: 7)
Microbiology and Immunology     Hybrid Journal   (Followers: 10)
Molecular Immunology     Hybrid Journal   (Followers: 17)
Mucosal Immunology     Hybrid Journal   (Followers: 6)
Nature Immunology     Full-text available via subscription   (Followers: 309)
Nature Reviews Immunology     Full-text available via subscription   (Followers: 293)
Neuroimmunology and Neuroinflammation     Open Access   (Followers: 3)
NeuroImmunoModulation     Full-text available via subscription   (Followers: 2)
Neurology : Neuroimmunology & Neuroinflammation     Open Access   (Followers: 4)
npj Vaccines     Hybrid Journal  
OA Immunology     Open Access  
Ocular Immunology & Inflammation     Hybrid Journal   (Followers: 9)
OncoImmunology     Full-text available via subscription   (Followers: 3)
Open Allergy Journal     Open Access  
Open Cancer Immunology Journal     Open Access  
Open Forum Infectious Diseases     Open Access   (Followers: 4)
Open Immunology Journal     Open Access  
Open Journal of Immunology     Open Access   (Followers: 5)
Open Virology Journal     Open Access  
Oral Microbiology and Immunology     Hybrid Journal   (Followers: 1)
Papillomavirus Research     Open Access  
Parasite Immunology     Hybrid Journal   (Followers: 3)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 38)
Perspectives in Vaccinology     Open Access   (Followers: 1)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 3)
Polish Pneumonology and Allergology     Open Access   (Followers: 1)
Procedia in Vaccinology     Open Access   (Followers: 2)
Recent Patents on Inflammation & Allergy Drug Discovery     Hybrid Journal   (Followers: 2)
Research & Reviews : A Journal of Immunology     Full-text available via subscription   (Followers: 6)
Research Journal of Allergy     Open Access   (Followers: 3)
Research Journal of Immunology     Open Access   (Followers: 3)
Results in Immunology     Open Access   (Followers: 4)
Revista Alergia México     Open Access  
Revista Portuguesa de Imunoalergologia     Open Access   (Followers: 2)
Revue Française d'Allergologie     Full-text available via subscription   (Followers: 3)
Russian Journal of Infection and Immunity     Open Access   (Followers: 20)
Scandinavian Journal of Immunology     Hybrid Journal   (Followers: 10)
Science Immunology     Full-text available via subscription   (Followers: 16)
Self/Nonself - Immune Recognition and Signaling     Full-text available via subscription   (Followers: 2)
Seminars in Immunology     Hybrid Journal   (Followers: 13)
Seminars in Immunopathology     Hybrid Journal   (Followers: 3)
Sinusitis     Open Access  
South East European Journal of Immunology     Open Access  
Therapeutic Advances in Vaccines     Hybrid Journal   (Followers: 1)
Therapeutic Advances in Vaccines and Immunotherapy     Open Access  
Toxicology and Environmental Health Sciences     Hybrid Journal   (Followers: 6)
Transactions of the Royal Society of Tropical Medicine and Hygiene     Hybrid Journal   (Followers: 4)
Transplant Immunology     Hybrid Journal   (Followers: 8)
Transplantation     Hybrid Journal   (Followers: 20)
Trends in Immunology     Full-text available via subscription   (Followers: 54)

        1 2 | Last

Similar Journals
Journal Cover
Clinical Immunology
Journal Prestige (SJR): 1.478
Citation Impact (citeScore): 3
Number of Followers: 25  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1521-6616 - ISSN (Online) 1521-7035
Published by Elsevier Homepage  [3206 journals]
  • Vedolizumab therapy in common variable immune deficiency associated
           enteropathy: A case series
    • Abstract: Publication date: Available online 11 February 2020Source: Clinical ImmunologyAuthor(s): Travis Sifers, Robert Hirten, Saurabh Mehandru, Huai-Bin Mabel Ko, Jean-Frederic Colombel, Charlotte Cunningham-RundlesAbstractA number of gastrointestinal complications occur in common variable immunodeficiency (CVID). Infections are one cause, but various forms of severe non-infectious enteropathy also lead to substantial morbidity. The presence of T cell lymphocytic infiltrates in the mucosa have suggested that vedolizumab, a humanized monoclonal antibody which binds to alpha4 beta7 integrin and inhibits the migration of effector T-lymphocytes into gastrointestinal tissues, would be an effective treatment. A previous report of 3 CVID cases suggested benefit in 2 subjects. In this study 7 CVID patients with severe enteropathy were treated with vedolizumab. Four of the 7 completed vedolizumab induction therapy but 3 subjects had acute decompensation during induction and treatment was stopped. While one subject showed improvement, 6 of the 7 patients were withdrawn from therapy. While vedolizumab may be of use in some CVID subjects, it was not ultimately found helpful in most of these patients.
       
  • Common innate pathways to autoimmune disease
    • Abstract: Publication date: Available online 10 February 2020Source: Clinical ImmunologyAuthor(s): David Langan, Kamal D. Moudgil, Noel R. RoseAbstractUntil recently, autoimmune disease research has primarily been focused on elucidating the role of the adaptive immune system. In the past decade or so, the role of the innate immune system in the pathogenesis of autoimmunity has increasingly been realized. Recent findings have elucidated paradigm-shifting concepts, for example, the implications of “trained immunity” and a dysbiotic microbiome on the susceptibility of predisposed individuals to clinical autoimmunity. In addition, the application of modern technologies such as the quantum dot (Qdot) system and ‘Omics’ (e.g., genomics, proteomics, and metabolomics) data-processing tools has proven fruitful in revisiting mechanisms underlying autoimmune pathogenesis and in identifying novel therapeutic targets. This review highlights recent findings discussed at the American Autoimmune-Related Disease Association (AARDA) 2019 colloquium. The findings covering autoimmune diseases and autoinflammatory diseases illustrate how new developments in common innate immune pathways can contribute to the better understanding and management of these immune-mediated disorders.
       
  • B cells in rheumatoid arthritis synovial tissues encode focused antibody
           repertoires that include antibodies that stimulate macrophage TNF-α
           production
    • Abstract: Publication date: Available online 5 February 2020Source: Clinical ImmunologyAuthor(s): Serra E. Elliott, Sarah Kongpachith, Nithya Lingampalli, Julia Z. Adamska, Bryan J. Cannon, Lisa K. Blum, Michelle S. Bloom, Matthew Henkel, Mandy J. McGeachy, Larry W. Moreland, William H. RobinsonAbstractRheumatoid arthritis (RA) is characterized by the production of anti-citrullinated protein antibodies (ACPAs). To gain insights into the relationship between ACPA-expressing B cells in peripheral blood (PB) and synovial tissue (ST), we sequenced the B cell repertoire in paired PB and ST samples from five individuals with established, ACPA+ RA. Bioinformatics analysis of paired heavy and light chain sequences revealed clonally-related family members shared between PB and ST. ST-derived antibody repertoires exhibited reduced diversity and increased normalized clonal family size compared to PB-derived repertoires. Functional characterization showed that seven recombinant antibodies (rAbs) expressed from subject-derived sequences from both compartments bound citrullinated antigens and immune complexes (ICs) formed using one ST-derived rAb stimulated macrophage TNF-α production. Our findings demonstrate B cell trafficking between PB and ST in subjects with RA and ST repertoires include B cells that encode ACPA capable of forming ICs that stimulate cellular responses implicated in RA pathogenesis.
       
  • Cost and impact of early diagnosis in primary immunodeficiency disease: A
           literature review
    • Abstract: Publication date: Available online 5 February 2020Source: Clinical ImmunologyAuthor(s): Kim Elsink, Joris M. van Montfrans, Mariëlle E. van Gijn, Maartje Blom, P. Martin van Hagen, T.W. Kuijpers, Geert W.J. FrederixAbstractBackgroundNew, innovative, costly diagnostic methods for patients with primary immunodeficiencies (PID) demand upfront insight into their potential cost savings and added value for individual patients. As such, high quality, comparable economic evaluations are of utmost importance to enable informed decisions. The objective of this review was therefore to create an extensive overview of current costing studies and potential cost savings of early diagnosis in primary immunodeficiency disease.MethodsA literature search in PubMed was conducted and studies involving any form of costing study in the field of PIDs were included. Of the included studies, study characteristics, cost parameters and benefits of early diagnosis were extracted and outlined in separate tables.ResultsTwenty two studies met the inclusion criteria and were included in the review. The papers were categorized according to their subject: neonatal screening for severe combined immunodeficiency (SCID), Ig replacement therapies and studies reporting on costs of general or specific PIDs. Within and between these groups variability in reported costing characteristics was observed. In studies that reported cost savings pre- and post-diagnosis, cost savings ranged from 6500 to 108,463 USD of total costs per patient.ConclusionThis literature review shows that, regardless of what aspect of PIDs has been studied, in nearly all cases early diagnosis reduces health care consumption and leads to better health outcomes for patients with PIDs. We found considerable variability in costing characteristics of economic evaluations of PID patients, which hampers the comparability of outcomes. More effort is needed to create uniformity and define cost parameters in economic evaluations in the field of PIDs, facilitating further prospective research to extensively assess the benefits of early diagnosis.
       
  • Mercury-induced autoimmunity: Drifting from micro to macro concerns on
           autoimmune disorders
    • Abstract: Publication date: Available online 4 February 2020Source: Clinical ImmunologyAuthor(s): Geir Bjørklund, Massimiliano Peana, Maryam Dadar, Salvatore Chirumbolo, Jan Aaseth, Natália MartinsAbstractMercury (Hg) is widely recognized as a neurotoxic metal, besides it can also act as a proinflammatory agent and immunostimulant, depending on individual exposure and susceptibility. Mercury exposure may arise from internal body pathways, such as via dental amalgams, preservatives in drugs and vaccines, and seafood consumption, or even from external pathways, i.e., occupation, environmental pollution, and handling of metallic items and cosmetics containing Hg. In susceptible individuals, chronic low Hg exposure may trigger local and systemic inflammation, even exacerbating the already existing autoimmune response in patients with autoimmunity. Mercury exposure can trigger dysfunction of the autoimmune responses and aggravate immunotoxic effects associated with elevated serum autoantibodies titers. The purpose of the present report is to provide a critical overview of the many issues associated with Hg exposure and autoimmunity. In addition, the paper also focuses on individual susceptibility and other health effects of Hg.
       
  • Interactions of viruses and the humoral innate immune response
    • Abstract: Publication date: Available online 4 February 2020Source: Clinical ImmunologyAuthor(s): Bailey E. Maloney, Krishani Dinali Perera, Danielle R.D. Saunders, Naemi Shadipeni, Sherry D. FlemingAbstractThe innate immune response is crucial for defense against virus infections where the complement system, coagulation cascade and natural antibodies play key roles. These immune components are interconnected in an intricate network and are tightly regulated to maintain homeostasis and avoid uncontrolled immune responses. Many viruses in turn have evolved to modulate these interactions through various strategies to evade innate immune activation. This review summarizes the current understanding on viral strategies to inhibit the activation of complement and coagulation cascades, evade natural antibody-mediated clearance and utilize complement regulatory mechanisms to their advantage.
       
  • MicroRNA-9 ameliorates destructive arthritis through down-regulation of
           NF-κB1-RANKL pathway in fibroblast-like synoviocytes
    • Abstract: Publication date: March 2020Source: Clinical Immunology, Volume 212Author(s): Wen Shi Lee, Shinsuke Yasuda, Michihiro Kono, Yuki Kudo, Sanae Shimamura, Michihito Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Tomohiro Shimizu, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya AtsumiWe investigated the effect of miR-9 on fibroblast-like synoviocytes (FLS) from RA patients and animal arthritis model. The binding of miR-9 to NF-κB1 3’UTR was analyzed by luciferase reporter assay and immunoprecipitation. ChIP assay and luciferase promoter assay were performed to identify the binding of NF-κB1 to RANKL promoter and its activity. FLS were treated with miR-9/anti-miR-9 to evaluate cell proliferation and the expression of RANKL. Therapeutic effect of intra-articular miR-9 was evaluated in type-II collagen-induced arthritis in rats. miR-9 bound to the 3’-UTR of NF-κB1 and downregulated NF-κB1. NF-κB1 bound to RANKL promoter and increased the promoter activity of RANKL. RANKL was downregulated by miR-9. Proliferation of FLS was increased by miR-9 inhibitor. miR-9 dampened experimental arthritis by lowering inflammatory state, reducing RANKL and osteoclasts formation. Our findings revealed miR-9-NF-κB1-RANKL pathway in RA-FLS, further, miR-9 ameliorated inflammatory arthritis in vivo which propose therapeutic implications of miR- 9 in RA.Graphical abstractKnown: miR-9 has lower expression in arthritis cartilage tissue. Normally, miR-9 binds to NF-κB1 or protegenin and promotes the survival and proliferation rate of chondrocyte as well as inhibits apoptosis. Loss of miR-9 will against this progress and hence reduce the cell numbers of chondrocytes [14,33]. However, miR-9 could also bind to MCPIP and upregulate the IL-6 expression which is the main cytokines in the progression of arthritis [35]. Bone fracture in vivo study has lower miR-9 expression which can promote the osteoclast precursor migration and increase the survival of osteoclast [34]. TNF-α induces IL-6 expression and the combination of IL-6/sIL-6R directly increases the expression of RANKL in RA-FLS [28]. Novel: In our study, we discover the role of NF-κB1 as one of the transcription factors to RANKL promoter, i.e. TNF-α and IFN-γ synergistically activates NF-κB signaling and hence upregulates RANKL expression in mRNA levels and protein levels (purple arrows). MiR-9 binds to NF-κB1 3’UTR and suppresses translational effect or cleaves NF-κB1 mRNA therefore suppresses the downstream of NF-κB1 signaling (red arrows). NF-κB1/p105 is processed by proteasome and produces NF-κB1/p50 which then enters the nucleus and acts as a transcription factor. RANKL expression and inflammation of RA are then indirectly downregulated by miR-9. Inhibiting miR-9 increases the proliferation of RA-FLS, which contributes to the pathophysiology of RA (green arrow)IL-6: interleukin-6; MCPIP: monocyte chemoattractant protein-induced protein 1; NF-κB1: nuclear factor kappa B; RA-FLS: rheumatoid arthritis fibroblast-like synoviocytes; RANKL: receptor activator nuclear factor kappa b ligand.Unlabelled Image
       
  • The binding of SLE autoantibodies to mitochondria
    • Abstract: Publication date: Available online 24 January 2020Source: Clinical ImmunologyAuthor(s): David S. Pisetsky, Diane M. Spencer, Fariborz Mobarrez, Enrico Fuzzi, Iva Gunnarsson, Elisabet SvenungssonAbstractSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by immune complexes. Because these complexes contain mitochondrial components, we assessed the presence of antibodies to whole mitochondria (wMITO) using an ELISA in which mitochondria from mouse liver are bound to microtiter plates pre-coated with poly-l-lysine. Studies with this ELISA demonstrated that SLE plasmas contain abundant anti-wMITO activity. While digestion with DNase 1 did not affect anti-wMITO activity, adsorption of plasma on DNA affinity columns could reduce binding activity. Assay for anti-mitochondrial antibodies (AMA) by immunofluorescence and an ELISA with the M2 antigen (2-oxo-acid dehydrogenase protein complex) showed a low frequency of positivity, indicating that AMA and anti-wMITO are distinct specificities. In the study of 204 patients with SLE, the levels of anti-wMITO were higher in active SLE and correlated with levels of anti-DNA. These findings suggest that anti-wMITO can form immune complexes with mitochondria which may drive pathogenesis.
       
  • The role of protein disulphide-isomerase A3 as autoantigen in the
           pathogenesis of autoimmune thyroiditis and related brain damage in adult
           mice
    • Abstract: Publication date: Available online 23 January 2020Source: Clinical ImmunologyAuthor(s): Wenqing Yang, Yang Xiang, Hongmei Zhang, Zhongyan Shan, Jing Li, Weiping TengAbstractAutoimmune thyroiditis (AIT)-related brain damage is one of most severe extrathyroidal manifestations of AIT, but the mechanism remains unclear. In this study, we confirmed that protein disulfide-isomerase A3 (PDIA3) is expressed in both thyroid and brain tissues of mouse, and found the significantly increased serum levels of anti-PDIA3 antibody (PDIA3Ab) in classical mouse models of thyroiditis. In addition, we investigated the PDIA3-specific autoimmune reaction in thyroid and brain tissues in a mouse model with high–serum PDIA3Ab induced by immunization with recombinant PDIA3 protein. PDIA3-immunized mice had elevated serum thyrotropin and impaired learning and memory. PDIA3-expressing cells had IgG deposition, and IgG colocalized with C3 in the thyroid and brain tissues of PDIA3-immunized mice, resulting in membrane attack complex formation. Our results suggest that PDIA3 protein may be a common autoantigen shared by the thyroid and brain tissues and involve in the thyroidal and intracerebral damage through activating complement system.
       
  • Case report on mesangial proliferative glomerulonephritis with
           multicentric Castleman's disease: Approach to the onset mechanism of
           immunoglobulin A nephropathy
    • Abstract: Publication date: Available online 21 January 2020Source: Clinical ImmunologyAuthor(s): Kazunori Karasawa, Shota Ogura, Yoei Miyabe, Kenichi Akiyama, Kosaku Nitta, Takahito MoriyamaAbstractGalactose-deficient immunoglobulin A1 (Gd-IgA1) was recently identified as a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN). Gd-IgA1 is produced by the mucosal immune system. IgAN is thought to develop because of the deposition of a circulating immune-complex containing Gd-IgA1 in the kidney. Multicentric Castleman's disease (MCD) is a rare non-neoplastic lymphoproliferative disorder. As an etiology model, hypercytokinemia, including increased levels of interleukin-6, is the primary pathogenesis of many MCD cases. Here, we present two cases of mesangial proliferative glomerulonephritis with MCD. According to renal biopsy findings, one was diagnosed with non-IgAN and the other with IgAN. Surprisingly, in both cases, Gd-IgA1 was produced by plasma cells in the lymph nodes, suggesting that Gd-IgA1 production alone does not cause IgAN; rather, it may be produced without induction by mucosal immunity. Our findings demonstrate the diversity of the development of IgAN and help to reconsider the onset mechanism of IgAN.
       
  • Corrigendum to “Flow cytometric assessment of leukocyte kinetics for the
           monitoring of tissue damage” [Clin Immunol 2018; 197: 224–230]
    • Abstract: Publication date: Available online 20 January 2020Source: Clinical ImmunologyAuthor(s): Wouter B.L. van den Bossche, Kyrill Rykov, Cristina Teodosio, Bas L.E.F. ten Have, Bas A.S. Knobben, Maurits S. Sietsma, Karin Josiassen, Sandra de Bruin-Versteeg, Alberto Orfao, Jacques J.M. van Dongen, Jos J.A.M. van Raay
       
  • Impairment of agonist-induced M2 muscarinic receptor activation by
           autoantibodies from chagasic patients with cardiovascular dysautonomia
    • Abstract: Publication date: Available online 16 January 2020Source: Clinical ImmunologyAuthor(s): Sabrina P. Beltrame, Laura C. Carrera Páez, Sergio R. Auger, Ahmad H. Sabra, Claudio R. Bilder, Claudia I. Waldner, Juan C. GoinPrevious studies showed that circulating autoantibodies against M2 muscarinic receptors (anti-M2R Ab) are associated with decreased cardiac parasympathetic modulation in patients with chronic Chagas disease (CD). Here we investigated whether the exposure of M2R to such antibodies could impair agonist-induced receptor activation, leading to the inhibition of associated signaling pathways. Preincubation of M2R-expressing HEK 293T cells with serum IgG fractions from chagasic patients with cardiovascular dysautonomia, followed by the addition of carbachol, resulted in the attenuation of agonist-induced Gi protein activation and arrestin-2 recruitment. These effects were not mimicked by the corresponding Fab fractions, suggesting that they occur through receptor crosslinking. IgG autoantibodies did not enhance M2R/arrestin interaction or promote M2R internalization, suggesting that their inhibitory effects are not likely a result of short-term receptor regulation. Rather, these immunoglobulins could function as negative allosteric modulators of acetylcholine-mediated responses, thereby contributing to the development of parasympathetic dysfunction in patients with CD.Graphical abstractUnlabelled Image
       
  • Baseline derived neutrophil-to-lymphocyte ratio as a prognostic biomarker
           for non-colorectal gastrointestinal cancer patients treated with immune
           checkpoint blockade
    • Abstract: Publication date: Available online 15 January 2020Source: Clinical ImmunologyAuthor(s): Shuang Li, Jianling Zou, Chang Liu, Xi Jiao, Jifang Gong, Jian Li, Zhenghang Wang, Ming Lu, Zhihao Lu, Lin ShenAbstractBackgroundBiomarkers in non-colorectal gastrointestinal (GI) cancer patients receiving immune checkpoint blockades (ICBs) are still limited.MethodsData were prospectively collected from a discovery cohort (n = 53) and a validation cohort (n = 107) in patients with non-colorectal GI cancer receiving ICB, as well as a chemotherapy-only cohort (n = 171). System inflammatory markers and derived neutrophil-to-lymphocyte ratio (dNLR) were determined as biomarkers by univariate and multivariate analyses.ResultsA higher level of dNLR (cutoff = 3) was associated with shorter overall survival (OS) in discovery and validation cohorts. In pooled cohort, disease control rate (DCR) (28% vs. 48.1%) was associated with dNLR (p = .017). In univariate analysis, original tumor site, tumor histopathology, number of metastases, and dNLR were correlated with OS. In multivariate analysis, higher dNLR level was correlated with reduced OS (10.43 months vs. 4.20 months, p 
       
  • The increased IL-17-producing γδT cells promote tumor cell proliferation
           and migration in neuroblastoma
    • Abstract: Publication date: Available online 10 January 2020Source: Clinical ImmunologyAuthor(s): Hui Zhang, Wenjia Chai, Wei Yang, Wei Han, Wenjun Mou, Yue Xi, Xi Chen, Hui Wang, Wei Wang, Hong Qin, Huanmin Wang, Xiaoli Ma, Xiaolin Wang, Jingang GuiAbstractNeuroblastoma (NB) is the most common solid extracranial malignancy in children with a considerable chance of metastatic progression. Prevalent evidence supports the anti-tumor role of γδT cells and these cells have been testing in clinical trials for constraining tumor growth. A small subpopulation of γδT cells releasing IL-17, however, were demonstrated to exert tumor-promoting effects in many aspects. In this study, we found an augment of IL-17+ γδT cells both in in vitro PAM-stimulated γδT-cell expanding culture and circulating γδT cells in NB patients. These patient-origin cells expanded in vitro by PAM in the presence of IL-17 polarizing condition were shown to promote the proliferation and migration of NB cells. Furthermore, an intrinsic preference for IL-17 polarization in NB γδT cells was revealed by mRNA microarray and Western Blot, which pointed to an up-regulated expression of multiple Th17-development related genes in addition to an increased phosphorylation level of STAT3.
       
  • Longitudinal relationships between rheumatoid factor and cytokine
           expression by immunostimulated peripheral blood lymphocytes from patients
           with rheumatoid arthritis: New insights into B-cell activation
    • Abstract: Publication date: Available online 8 January 2020Source: Clinical ImmunologyAuthor(s): John M. Davis, Cynthia S. Crowson, Keith L. Knutson, Sara J. Achenbach, Michael A. Strausbauch, Terry M. Therneau, Eric L. Matteson, Sherine E. Gabriel, Peter J. WettsteinAbstractTo identify associations between immunostimulated cytokine production and disease characteristics, peripheral blood lymphocytes were collected from 155 adult patients with rheumatoid arthritis (RA) before and after a 5-year interval. The lymphocytes were activated in vitro with T-cell stimulants, cytosine-phosphate-guanine (CpG) oligonucleotide, and medium alone (negative control). Expression of 17 cytokines was evaluated with immunoassays, and factor analysis was used to reduce data complexity and identify cytokine combinations indicative of cell types preferentially activated by each immunostimulant. The findings showed that the highest numbers of correlations were between cytokine levels and rheumatoid factor (RF) positivity and between cytokine levels and disease duration. Scores for cytokines driven by CpG and medium alone were negatively associated with RF positivity and disease duration at baseline but positively associated with both at 5 years. Our findings suggest that RF expression sustained over time increases activation of B cells and monocytes without requirements for T-cell functions.
       
  • The immunologic features of patients with early-onset and polyautoimmunity
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Kacie J. Hoyt, Talal A. Chatila, Luigi D. Notarangelo, Melissa M. Hazen, Erin Janssen, Lauren A. HendersonAbstractInflammatory conditions are increasingly described in patients with primary immunodeficiencies; however, little is known about the prevalence of immune defects in patients who present first with autoimmunity. We describe the immunologic features of children with early-onset/polyautoimmunity followed in the Multiple Autoimmunity and Immunodeficiency (MAID) Clinic, where patients are co-managed by rheumatologists and immunologists. The most common autoimmune manifestations were cytopenias, lymphoproliferation, and colitis. Recurrent infections were noted in 65% of patients. Abnormalities in lymphocyte subsets and immunoglobulins were common. A pathogenic variant was identified in 19% of patients, and 2 novel inherited disorders were discovered. Additionally, 42% of patients had treatment changes implemented in the MAID clinic. By evaluating this unique cohort of patients, we report on the immunologic underpinning of early-onset/polyautoimmunity. The high rate of genetic diagnoses and treatment interventions in this population highlights the value of collaboration between rheumatologists and immunologists in the care of these complex patients.
       
  • High-dose intravenous methylprednisolone in juvenile non-infectious
           uveitis: A retrospective analysis
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Anja Schnabel, Elisabeth Unger, Normi Brück, Reinhard Berner, Ursula Range, Annette Holl-Wieden, Henner Morbach, Anna Leszczynska, Viktoria Bau, Christian M. HedrichAbstractNon-infectious uveitis is associated with visual impairment and blindness. Non-biologic treatment for non-infectious uveitis is not based on strong evidence. A retrospective chart review was conducted to investigate treatment response to high-dose intravenous methylprednisolone (IVMP) in children with non-infectious uveitis.Fifty-six patients (93 eyes affected) were included. In 29% uveitis was associated with juvenile idiopathic arthritis. Uveitis predominately affected the anterior segment, was bilateral and recurrent. Complications were common and included visual loss, synechiae, cataract and/or retinal lesions. Patients received up to 5 IVMP at monthly intervals. Visual acuity improved at 3 and 6 months. Anterior chamber cells, synechiae, keratic precipitates, papillary and/or macular edema improved at 3 months. Children treated with ≥3 IVMP (vs 1 IVMP) experienced trends towards fewer relapses, fewer cataracts and less frequently required treatment with biologic agents.High-dose IVMP induce rapid improvement in children with non-infectious uveitis. Prospective randomized trials are required to confirm results.
       
  • Pre-transplant assessment of pp65-specific CD4 T cell responses identifies
           CMV-seropositive patients treated with rATG at risk of late onset
           infection
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Maria O. López-Oliva, Virginia Martínez, Aranzazu Rodríguez-Sanz, Laura Álvarez, M. José Santana, Rafael Selgas, Carlos Jiménez, Teresa BellónAbstractAssessment of CMV-specific T cell immunity might be a useful tool in predicting CMV infection after solid organ transplantation. We have investigated CD4 and CD8 T-cell responses to CMV pp65 and IE-1 antigens in a prospective study of 28 CMV-seropositive kidney transplant recipients who were administered lymphocyte-depleting antibodies (Thymoglobulin®) as induction treatment and with universal prophylaxis for CMV infection. The response was analyzed by intracellular flow cytometry analysis of IFN-γ production in pretransplant samples and at 1, 6, 12 and 24 months post-transplant. Overall, only pretransplant CD4 T-cell responses to pp65 were significantly lower (p = .004) in patients with CMV replication post-transplant. ROC curve analysis showed that pre-transplant frequencies of pp65-specific CD4 + T cells below 0.10% could predict CMV infection with 75% sensitivity and 83.33% specificity (AUC: 0.847; 95% CI: 0.693–1.001; p = .0054) and seem to be mandatory for efficient control of CMV viral replication by the host immune system. In conclusion, the functional assessment of CMV-specific CD4 T-cell immunity pretransplant in seropositive patients may allow the identification of Thymoglobulin®-treated kidney transplant recipients at risk of developing CMV infection post-transplantation.
       
  • Chronic granulomatous disease: Single-center Spanish experience
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): A. Robles-Marhuenda, J. Álvarez-Troncoso, R. Rodríguez-Pena, C. Busca-Arenzana, E. López-Granados, F. Arnalich-Fernández
       
  • Signal inhibitory receptor on leukocytes (SIRL)-1 and leukocyte-
           associated immunoglobulin-like receptor (LAIR)-1 regulate neutrophil
           function in infants
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Sjanna B. Besteman, Amie Callaghan, Marije P. Hennus, Geertje H.A. Westerlaken, Linde Meyaard, Louis L. BontAbstractDuring severe respiratory syncytial virus (RSV) bronchiolitis there is a massive influx of activated neutrophils to the lungs. An exaggerated immune response contributes to lung damage and disease severity during RSV infection. We have previously shown that normal adult neutrophil function can be modulated by agonists of SIRL-1. Here we aimed to measure the potential of two immune checkpoints: SIRL-1 and LAIR-1, to regulate the function of fresh blood and sputum neutrophils from infants with and without severe RSV bronchiolitis. We show a modest inhibition of the oxidative burst through SIRL-1 and LAIR-1, in control and RSV-infected infants. In addition, SIRL-1 and LAIR-1 inhibited neutrophil extracellular traps (NET) formation by sputum neutrophils of RSV patients. Altogether our data show that inhibitory receptors LAIR-1 and SIRL-1 can be used to regulate neutrophil function.
       
  • Juvenile idiopathic arthritis-associated uveitis
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Ethan S. Sen, A.V. RamananAbstractJuvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in children and JIA-associated uveitis its most frequent extra-articular manifestation. The uveitis is potentially sight-threatening and so carries a considerable risk of morbidity. The commonest form of uveitis seen in JIA is chronic anterior uveitis which is almost always asymptomatic in the initial stages. Therefore, screening for JIA-associated uveitis in at-risk patients is essential. The aim of early detection and treatment is to minimise intra-ocular inflammation and avoid complications leading to visual loss, resulting from both disease activity and medications. There is increasing evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. Two randomised controlled trials of adalimumab in JIA-associated uveitis provide convincing evidence for the use of this biologic in patients who fail to respond adequately to methotrexate. Tocilizumab and baricitinib are being investigated as alternatives to anti-tumour necrosis factor drugs.
       
  • A novel de novo NLRC4 mutation reinforces the likely pathogenicity of
           specific LRR domain mutation
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Chai Teng Chear, Revathy Nallusamy, Scott W. Canna, Kwai Cheng Chan, Mohd Farid Baharin, Munirah Hishamshah, Hamidah Ghani, Adiratna Mat Ripen, Saharuddin Bin MohamadAbstractAutoinflammatory disorders are characterized by dysregulated innate immune response, resulting in recurrent uncontrolled systemic inflammation and fever. Gain-of-function mutations in NLRC4 have been described to cause a range of autoinflammatory disorders. We report a twelve-year-old Malay girl with recurrent fever, skin erythema, and inflammatory arthritis. Whole exome sequencing and subsequent bidirectional Sanger sequencing identified a heterozygous missense mutation in NLRC4 (NM_001199138: c.1970A> T). This variant was predicted to be damaging in silico, was absent in public and local databases and occurred in a highly conserved residue in the leucine-rich repeat (LRR) domain. Cytokine analysis showed extremely high serum IL-18 and IL-18/CXCL9 ratio, consistent with other NLRC4-MAS patients. In summary, we identified the first patient with a novel de novo heterozygous NLRC4 gene mutation contributing to autoinflammatory disease in Malaysia. Our findings reinforce the likely pathogenicity of specific LRR domain mutations in NLRC4 and expand the clinical spectrum of NLRC4 mutations.
       
  • IL-6 is present in beta and alpha cells in human pancreatic islets:
           Expression is reduced in subjects with type 1 diabetes
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Sakthi Rajendran, Florence Anquetil, Estefania Quesada-Masachs, Madeleine Graef, Nathaly Gonzalez, Sara McArdle, Tiffany Chu, Lars Krogvold, Knut Dahl-Jørgensen, Matthias von HerrathAbstractIL-6 is a pro-inflammatory cytokine upregulated in some autoimmune diseases. The role of IL-6 in the development of type 1 diabetes (T1D) is unclear. Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D. However, in some rodent models and isolated human islets, IL-6 has been found to have a protective role for beta cells by reducing oxidative stress. Hence, we systematically investigated local tissue expression of IL-6 in human pancreas from non-diabetic, auto-antibody positive donors and donors with T1D and T2D. IL-6 was constitutively expressed by beta and alpha cells regardless of the disease state. However, expression of IL-6 was highly reduced in insulin-deficient islets of donors with T1D, and the expression was then mostly restricted to alpha cells. Our findings suggest that the implication of IL-6 in T1D pathogenesis might be more complex than previously assumed.
       
  • Morbidity in an adenosine deaminase-deficient patient during 27 years of
           enzyme replacement therapy
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Eyal Grunebaum, Brenda Reid, Ahmed Naqvi, Michael S. Hershfield, Vy Hong-Diep Kim, Matthew P. Muller, Lisa K. Hicks, Erika Lee, Stephen Betschel, Chaim M. RoifmanAbstractIntroductionAdenosine deaminase (ADA) deficiency causes severe immunodeficiency that is lethal in infancy. Enzyme replacement therapy (ERT) can improve the metabolic, immune and non-immune abnormalities in patients prior to transplantation, however, its benefits over extended periods are not well characterized.We describe a 28-year-old female who received ERT for 27 years. She suffered from EBV negative B cell lymphoma of the hip at 14 years of age and Guillian-Barre Syndrome 2 years later. At 22 years of age, she experienced a gastrointestinal infection with Mycobacterium genavense. At 26 years of age, lymphoma reoccurred with multiple liver lesions followed by Mycobacterium genavense infection with dissemination to the brain. Throughout this period, ADA activity in the plasma was within the therapeutic range. Repeated evaluations demonstrated very low lymphocyte counts and impaired T cell function.ConclusionsERT might be insufficient to maintain normal immunity over extended periods in some ADA-deficient patients.
       
  • Childhood GPA, EGPA, and MPA
    • Abstract: Publication date: February 2020Source: Clinical Immunology, Volume 211Author(s): Mehul Jariwala, Ronald M. LaxerAbstractAntineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a term used to describe rare primary systemic vasculitides affecting small and medium-sized blood vessels. AAV diseases which include Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA), Microscopic Polyangiitis (MPA) and renal limited ANCA vasculitis. These multisystemic disorders involve upper and lower respiratory tract and kidneys associated with organ damage and long term sequelae. Newer understanding of pathogenesis in AAV have paved the way for clinical research with different biologic therapies. In spite of the paucity of clinical trials in pediatric AAV, the long-term survival of patients with AAV has improved dramatically. International collaborations will help to conduct clinical trials in pediatric AAV and help in better understanding of remission rates, relapse rates, and other outcomes. This article aims to provide a comprehensive review of pediatric AAV with a focus on epidemiology, disease pathogenesis, treatment trials, and prognosis.
       
  • Predictive value of mesangial C3 and C4d deposition in IgA nephropathy
    • Abstract: Publication date: Available online 31 December 2019Source: Clinical ImmunologyAuthor(s): Ki Heon Nam, Young Su Joo, Changhyun Lee, Sangmi Lee, Joohwan Kim, Hae-Ryong Yun, Jung Tak Park, Tae Ik Chang, Dong-Ryeol Ryu, Tae-Hyun Yoo, Ho Jun Chin, Shin-Wook Kang, Hyeon Joo Jeong, Beom Jin Lim, Seung Hyeok Han, on behalf of The Korean GlomeruloNEphritis sTudy (KogNET) GroupAbstractWe aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(
       
  • Eczematous dermatitis in primary immunodeficiencies: A review of cutaneous
           clues to diagnosis
    • Abstract: Publication date: Available online 30 December 2019Source: Clinical ImmunologyAuthor(s): Sidney Hoskins, Suzanne Skoda-Smith, Troy R. Torgerson, Markus D. BoosAbstractPrimary immunodeficiency Disorders (PIDD) are a varied group of heritable disorders characterized by defects in components of the innate and/or adaptive arms of the immune system. Although diagnosing these disorders is often challenging, the skin is a readily accessible and easily assessable organ that may provide clues to a diagnosis of PIDD. Specifically, many immunodeficiencies are associated with characteristic cutaneous eruptions that, based on their morphology, distribution and symptomatology, may suggest a specific underlying diagnosis. This review will discuss an approach to identifying and managing PIDDs that typically present with eczematous dermatitis.
       
  • Reduced PD-1 expression on circulating CXCR5+ and CXCR5− FOXP3+ Treg
           cells marks type 1 diabetes initiation in children
    • Abstract: Publication date: Available online 30 November 2019Source: Clinical ImmunologyAuthor(s): Andrea Vecchione, Jolanda Gerosa, Roberta Di Fonte, Tatiana Jofra, Cicalese Maria Pia, Vincenzo Napoleone, Elio Ippolito, Giuseppe Galvani, Francesca Ragogna, Angela Stabilini, Eleonora Bianconi, Pauline Grogan, Clara Bonura, Riccardo Bonfanti, Giulio Frontino, Rita Nano, Raffaela Melzi, Maurizio De Pellegrin, Andrea Laurenzi, Franco MeschiAbstractAutoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular Treg cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5+) and CXCR5− Treg cells in the blood of children with new onset T1D and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls. Blood CXCR5+ and CXCR5− Treg cells were higher in frequency children with new onset T1D and expressed reduced amounts of PD-1 as compared to controls. Interestingly, the proportion of circulating FOXP3+ Tregs expressing PD-1 was also reduced in AAb-positive at-risk children as compared to controls, suggesting its potential use as a biomarker of disease initiation.
       
  • Emerging molecular biomarkers for predicting therapy response in psoriatic
           arthritis: A review of literature
    • Abstract: Publication date: Available online 27 November 2019Source: Clinical ImmunologyAuthor(s): Juliëtte Pouw, Emmerik Leijten, Timothy Radstake, Marianne BoesAbstractPsoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory musculoskeletal disorder that affects ~0.1% of the population. PsA may severely impact quality-of-life and constitutes a significant economic burden on our health care system. While early effective treatment is deemed essential to prevent irreversible joint damage and functional impairment, not all patients respond to the same disease modifying anti-rheumatic drugs (DMARDs). DMARD options for PsA are rapidly evolving, yet only 50–60% of patients show a satisfactory response to their first-line DMARD therapy. Hence, there is an urgent medical need to predict which patients benefit from a particular treatment. To this end, molecular biomarkers capable of predicting therapeutic response are currently being scrutinized in clinical studies, that together should build a framework for clinical guidelines that improve personalized targeted treatment. In this review new developments within the field of biomarker discovery for predicting therapeutic response to DMARDs in PsA are examined.
       
  • Do we need a new classification of juvenile idiopathic arthritis'
    • Abstract: Publication date: Available online 6 November 2019Source: Clinical ImmunologyAuthor(s): Alan M. Rosenberg
       
  • Baricitinib experience on STING-associated vasculopathy with onset in
           infancy: A representative case from Turkey
    • Abstract: Publication date: Available online 15 October 2019Source: Clinical ImmunologyAuthor(s): Sibel Balci, Rabia Miray Kisla Ekinci, Adriana Almeida de Jesus, Raphaela Goldbach-Mansky, Mustafa YilmazAbstractStimulator of interferon genes associated vasculopathy with onset in infancy (SAVI), caused by heterozygote gain-of-function mutations in TMEM173, is characterized by fever attacks with ulcerating cutaneous manifestations on cold-sensitive areas and interstitial lung disease. A six-month-old boy was admitted to our hospital with fever, cough, and rash on the external surface of both upper and lower extremities. Respiratory symptoms consistent with ILD developed and skin lesions evolved to eschar formation particularly on acral regions. Ultimately, diagnosis of SAVI was confirmed at the age of 10 months due to the high level of interferon-score and a heterozygous N154S mutation in TMEM173. Since systemic corticosteroid and ruxolitinib were not effective, baricitinib was initiated at the age of 15 months, resulting in alleviation of fever attacks, cutaneous manifestations and respiratory symptoms within 2 months. In conclusion, we reported an infant diagnosed with SAVI at the age of 10 months and treated with baricitinib.
       
  • Toll-like receptor 3 (TLR3) variant and NLRP12 mutation confer
           susceptibility to a complex clinical presentation
    • Abstract: Publication date: Available online 21 August 2019Source: Clinical ImmunologyAuthor(s): Yuval Tal, Yaarit Ribak, Aya Khalaila, Oded Shamriz, Nofar Marcus, Adar Zinger, Vardiella Meiner, Ronen Schuster, Eli C. Lewis, Amit NahumAbstractGenetic aberrations in the toll-like receptor (TLR)3 pathway are associated with increased susceptibility to herpes simplex virus (HSV) infections. Leucine-rich repeat and PYD-containing protein (NLRP)12 is a component of the inflammasome apparatus, which is critical to an immediate innate inflammatory response. Aberrations in NLRP12 have been shown to mediate auto-inflammation. In this study, we present a 44-year old patient with severe HSV esophagitis and Crohn's disease. An immune and genetic investigation confirmed two coinciding genetic mutations in TLR3 and NLRP12. Our findings support conducting laboratory workup that targets TLR3 pathway in the immunocompetent host developing recurrent HSV infections.
       
  • Hypertension: An immune related disorder'
    • Abstract: Publication date: Available online 8 August 2019Source: Clinical ImmunologyAuthor(s): Eleni Sereti, Kimon S. Stamatelopoulos, Nikolaos A. Zakopoulos, Aikaterini Evangelopoulou, Clio P. Mavragani, Maria Eleftheria EvangelopoulosAbstractHypertension is a multifactorial disorder with serious complications and unknown etiology. Among potential contributors, immune dysregulation has been also proposed. The study population included 61 consecutive hypertensive patients and 55 healthy individuals of similar age and sex distribution. All study participants underwent a thorough evaluation for subclinical atherosclerosis and a full immunological profile including quantification of immunoglobulins (IgG, IgM, IgA) and lymphocyte subpopulations was obtained. Immunoglobulin levels IgG, IgA and IgM and complement factor C3 were found to be significantly increased in the hypertensive compared to the HC group while a statistically significant decrease in peripheral blood CD3+, CD4+ and CD8+ in hypertensive patients versus controls was detected. These findings might support a putative involvement of altered cellular and humoral immune responses in the pathogenesis of hypertension, implying a promising role for immunomodulatory strategies, already implemented in the treatment of autoimmune diseases, in the future management of hypertension.
       
  • A dominant activating RAC2 variant associated with
           immunodeficiency and pulmonary disease
    • Abstract: Publication date: Available online 2 August 2019Source: Clinical ImmunologyAuthor(s): B.M. Smits, P.H.C. Lelieveld, F.A. Ververs, M. Turkenburg, C. de Koning, M. van Dijk, H.L. Leavis, J.J. Boelens, C.A. Lindemans, A.C. Bloem, L. van de Corput, J. van Montfrans, S. Nierkens, M.E. van Gijn, D.P. Geerke, H.R. Waterham, L. Koenderman, M. Boes
       
  • The helminth-derived peptide GK-1 induces an anti-tumoral CD8 T cell
           response associated with downregulation of the PD-1/PD-L1 pathway
    • Abstract: Publication date: Available online 9 July 2019Source: Clinical ImmunologyAuthor(s): Noé Rodríguez-Rodríguez, Iris K. Madera-Salcedo, Emmanuel Bugarin-Estrada, Elizabeth Sánchez-Miranda, Diana Torres-García, Jacquelynne Cervantes-Torres, Gladis Fragoso, Florencia Rosetti, José C. Crispín, Edda SciuttoAbstractCD8 T cells can kill malignant cells in an antigen-specific manner. However, anti-tumoral responses are usually limited by suppressive factors that curb the effector responses of tumor-infiltrating CD8 T cells. Therapeutic strategies to overcome intra-tumoral T cell suppression, for example immune checkpoint inhibition, have been clinically effective in patients with cancer. Here, we provide data that demonstrates that GK-1, a peptide derived from the parasite Taenia crassiceps, promotes an anti-melanoma CD8 T cell response with heightened effector characteristics that leads to an increased amount of tumor-infiltrating CD44+ IFN-γ-producing CD8 T cells. The response induced by GK-1 was associated with a reduction in the expression of PD-1 and PD-L1 on tumor-infiltrating CD8 and dendritic cells, respectively, effects that led to a dramatic decrease in tumor burden. Our results suggest that the immunomodulatory properties of GK-1 may promote a CD8 T cell response that may be therapeutically useful in the setting of cancer.
       
  • Cellular immune responses against natural human papillomavirus infections
           among men in Kisumu, Kenya
    • Abstract: Publication date: Available online 2 May 2019Source: Clinical ImmunologyAuthor(s): R.O. Ondondo, E.A. Bukusi, Z.W. Ng'ang'a, M. Kiptoo, S. MpokeAbstractHuman papillomavirus (HPV) is associated with ano-genital and cervical cancer. Persistence of oncogenic HPV genotypes is a requirement for development and progression of malignancies. Although,>70% of women clear incident HPV infections, data on natural history and HPV immunology among men is limited. To evaluate cell-mediated immune responses to natural HPV infections among men, we assessed cytokine responses on PBMCs collected from men with persistent or cleared HPV. Men with HPV clearance and those with HPV persistence had increased odds (6-times and 3-times respectively) of mounting cytokine responses compared to HPV uninfected men. Th1 cytokines IFN-γ (5.1-fold) and IL-2 (4.2-fold) were significantly (p 
       
 
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