Please use this identifier to cite or link to this item:
doi:10.22028/D291-43622
Title: | Autoantibody mediated deficiency of IL-36-receptor antagonist in a subset of patients with psoriasis and psoriatic arthritis |
Author(s): | Hoffmann, Marie-Christin Fadle, Natalie Regitz, Evi Kos, Igor Age Cetin, Onur Lesan, Vadim Preuß, Klaus-Dieter Zaks, Marina Stöger, Elisabeth Zimmer, Vincent Klemm, Philipp Assmann, Gunter Pfeifer, Jochen Bittenbring, Joerg Thomas Bewarder, Moritz Vogt, Thomas Pföhler, Claudia Thurner, Bernhard Kessel, Christoph Thurner, Lorenz |
Language: | English |
Title: | Immunology Letters |
Volume: | 270 |
Publisher/Platform: | Elsevier |
Year of Publication: | 2024 |
Free key words: | Autoantibodies targeting the IL-36 receptor antagonist (IL-36Ra) occur in subgroups of patients with PsA and Pso IL-36Ra-autoantibodies deplete IL-36Ra serum/plasma level result in immunecomplex formation promote unrestricted IL-36 signal |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
Abstract: | 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. |
DOI of the first publication: | 10.1016/j.imlet.2024.106926 |
URL of the first publication: | https://www.sciencedirect.com/science/article/pii/S0165247824001007 |
Link to this record: | urn:nbn:de:bsz:291--ds-436228 hdl:20.500.11880/39080 http://dx.doi.org/10.22028/D291-43622 |
ISSN: | 1879-0542 0165-2478 |
Date of registration: | 2-Dec-2024 |
Description of the related object: | Supplementary materials |
Related object: | https://ars.els-cdn.com/content/image/1-s2.0-S0165247824001007-mmc1.docx |
Faculty: | M - Medizinische Fakultät |
Department: | M - Dermatologie M - Innere Medizin |
Professorship: | M - Prof. Dr. Stephan Stilgenbauer M - Dr. med. Lorenz Thurner M - Prof. Dr. Thomas Vogt |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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1-s2.0-S0165247824001007-main.pdf | 1,28 MB | Adobe PDF | View/Open |
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