Marie-Christin Hoffmann , Natalie Fadle , Evi Regitz , Igor Age Kos , Onur Cetin , Vadim Lesan , Klaus-Dieter Preuss , Marina Zaks , Elisabeth Stöger , Vincent Zimmer , Philipp Klemm , Gunter Assmann , Jochen Pfeifer , Joerg Thomas Bittenbring , Moritz Bewarder , Thomas Vogt , Claudia Pföhler , Bernhard Thurner , Christoph Kessel , Lorenz Thurner
{"title":"银屑病和银屑病关节炎患者中由自身抗体介导的 IL-36 受体拮抗剂缺乏症","authors":"Marie-Christin Hoffmann , Natalie Fadle , Evi Regitz , Igor Age Kos , Onur Cetin , Vadim Lesan , Klaus-Dieter Preuss , Marina Zaks , Elisabeth Stöger , Vincent Zimmer , Philipp Klemm , Gunter Assmann , Jochen Pfeifer , Joerg Thomas Bittenbring , Moritz Bewarder , Thomas Vogt , Claudia Pföhler , Bernhard Thurner , Christoph Kessel , Lorenz Thurner","doi":"10.1016/j.imlet.2024.106926","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Psoriatic arthritis (PsA) is known as a seronegative form of spondylarthropathy. The interleukin-36 cytokine family may have a major role in disease pathogenesis and particularly the related cutaneous manifestations. In light of our recent observations on (transient) autoantibody phenotypes neutralizing endogenous anti-inflammatory receptor antagonists (progranulin, IL-1Ra) in different inflammatory conditions, we set out to investigate the potential role of such antibodies targeting IL-36 cytokine family members in PsA and psoriasis without arthritic manifestations (Pso).</p></div><div><h3>Methods</h3><p>In the present study we screened for hypothetic autoantibodies against the anti-inflammatory mediators IL-36 receptor antagonist (IL-36Ra) and anti-inflammatory IL-38 in PsA, Pso and inflammatory and healthy controls. Serum samples of patients with PsA (<em>n</em> = 254), Pso (<em>n</em> = 100), systemic lupus erythematosus (SLE, <em>n</em> = 50), rheumatoid arthritis (RA, <em>n</em> = 100), ulcerative colitis (UC, <em>n</em> = 50), Crohn´s disease (CD, <em>n</em> = 50), and healthy controls (<em>n</em> = 237) were screened for autoantibodies against IL-36Ra and IL-38 as well as IL-36Ra levels by ELISA. Biochemical analysis for immune complexes and atypic protein isoforms as well as IL-36 signaling reporter assays were performed.</p></div><div><h3>Results</h3><p>Anti-IL-36Ra antibodies were detected in five out of 100 (5.0 %) patients with Pso, in 12 of 254 (4.72 %) patients with PsA and in one of 50 (2 %) patients with CD, but in none of the other investigated inflammatory or healthy controls. The IL-36Ra autoantibodies belonged to the IgG1 subclass and their titers ranged between 1:200 to 1:1600. They resulted in immune-complex formation, depletion of serum IL-36Ra levels and were functional in terms of facilitating unrestricted IL-36 signaling.</p></div><div><h3>Conclusion</h3><p>IL-36Ra autoantibodies were found in subgroups of patients with Pso and PsA and may drive respective pathology.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106926"},"PeriodicalIF":3.3000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824001007/pdfft?md5=93335ba1a513060ba43aaf9f1933485b&pid=1-s2.0-S0165247824001007-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Autoantibody mediated deficiency of IL-36-receptor antagonist in a subset of patients with psoriasis and psoriatic arthritis\",\"authors\":\"Marie-Christin Hoffmann , Natalie Fadle , Evi Regitz , Igor Age Kos , Onur Cetin , Vadim Lesan , Klaus-Dieter Preuss , Marina Zaks , Elisabeth Stöger , Vincent Zimmer , Philipp Klemm , Gunter Assmann , Jochen Pfeifer , Joerg Thomas Bittenbring , Moritz Bewarder , Thomas Vogt , Claudia Pföhler , Bernhard Thurner , Christoph Kessel , Lorenz Thurner\",\"doi\":\"10.1016/j.imlet.2024.106926\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>Psoriatic arthritis (PsA) is known as a seronegative form of spondylarthropathy. The interleukin-36 cytokine family may have a major role in disease pathogenesis and particularly the related cutaneous manifestations. In light of our recent observations on (transient) autoantibody phenotypes neutralizing endogenous anti-inflammatory receptor antagonists (progranulin, IL-1Ra) in different inflammatory conditions, we set out to investigate the potential role of such antibodies targeting IL-36 cytokine family members in PsA and psoriasis without arthritic manifestations (Pso).</p></div><div><h3>Methods</h3><p>In the present study we screened for hypothetic autoantibodies against the anti-inflammatory mediators IL-36 receptor antagonist (IL-36Ra) and anti-inflammatory IL-38 in PsA, Pso and inflammatory and healthy controls. Serum samples of patients with PsA (<em>n</em> = 254), Pso (<em>n</em> = 100), systemic lupus erythematosus (SLE, <em>n</em> = 50), rheumatoid arthritis (RA, <em>n</em> = 100), ulcerative colitis (UC, <em>n</em> = 50), Crohn´s disease (CD, <em>n</em> = 50), and healthy controls (<em>n</em> = 237) were screened for autoantibodies against IL-36Ra and IL-38 as well as IL-36Ra levels by ELISA. Biochemical analysis for immune complexes and atypic protein isoforms as well as IL-36 signaling reporter assays were performed.</p></div><div><h3>Results</h3><p>Anti-IL-36Ra antibodies were detected in five out of 100 (5.0 %) patients with Pso, in 12 of 254 (4.72 %) patients with PsA and in one of 50 (2 %) patients with CD, but in none of the other investigated inflammatory or healthy controls. The IL-36Ra autoantibodies belonged to the IgG1 subclass and their titers ranged between 1:200 to 1:1600. They resulted in immune-complex formation, depletion of serum IL-36Ra levels and were functional in terms of facilitating unrestricted IL-36 signaling.</p></div><div><h3>Conclusion</h3><p>IL-36Ra autoantibodies were found in subgroups of patients with Pso and PsA and may drive respective pathology.</p></div>\",\"PeriodicalId\":13413,\"journal\":{\"name\":\"Immunology letters\",\"volume\":\"270 \",\"pages\":\"Article 106926\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0165247824001007/pdfft?md5=93335ba1a513060ba43aaf9f1933485b&pid=1-s2.0-S0165247824001007-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunology letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0165247824001007\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunology letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165247824001007","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Autoantibody mediated deficiency of IL-36-receptor antagonist in a subset of patients with psoriasis and psoriatic arthritis
Objective
Psoriatic arthritis (PsA) is known as a seronegative form of spondylarthropathy. The interleukin-36 cytokine family may have a major role in disease pathogenesis and particularly the related cutaneous manifestations. In light of our recent observations on (transient) autoantibody phenotypes neutralizing endogenous anti-inflammatory receptor antagonists (progranulin, IL-1Ra) in different inflammatory conditions, we set out to investigate the potential role of such antibodies targeting IL-36 cytokine family members in PsA and psoriasis without arthritic manifestations (Pso).
Methods
In the present study we screened for hypothetic autoantibodies against the anti-inflammatory mediators IL-36 receptor antagonist (IL-36Ra) and anti-inflammatory IL-38 in PsA, Pso and inflammatory and healthy controls. Serum samples of patients with PsA (n = 254), Pso (n = 100), systemic lupus erythematosus (SLE, n = 50), rheumatoid arthritis (RA, n = 100), ulcerative colitis (UC, n = 50), Crohn´s disease (CD, n = 50), and healthy controls (n = 237) were screened for autoantibodies against IL-36Ra and IL-38 as well as IL-36Ra levels by ELISA. Biochemical analysis for immune complexes and atypic protein isoforms as well as IL-36 signaling reporter assays were performed.
Results
Anti-IL-36Ra antibodies were detected in five out of 100 (5.0 %) patients with Pso, in 12 of 254 (4.72 %) patients with PsA and in one of 50 (2 %) patients with CD, but in none of the other investigated inflammatory or healthy controls. The IL-36Ra autoantibodies belonged to the IgG1 subclass and their titers ranged between 1:200 to 1:1600. They resulted in immune-complex formation, depletion of serum IL-36Ra levels and were functional in terms of facilitating unrestricted IL-36 signaling.
Conclusion
IL-36Ra autoantibodies were found in subgroups of patients with Pso and PsA and may drive respective pathology.
期刊介绍：
Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings.
Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
