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

Files for this record:
File Description SizeFormat 
1-s2.0-S0165247824001007-main.pdf1,28 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons