Abstract
Objective: Raynaud's phenomenon (RP) is common in anti-RNP–positive patients with rheumatic diseases but is not itself known to be caused by autoimmunity. The aim of this study was to assess autoantibodies that could mediate this process. Methods: Antibodies derived from patient sera and from murine models of anti-RNP autoimmunity were screened for the ability to induce RP-like tissue ischemia and endothelial cell apoptosis in murine models and in vitro systems. Results: RNP-positive sera from RP patients and murine sera from RNP-positive B cell adoptive transfer recipients induced RP-like tissue ischemia and endothelial cell apoptosis. Proteomic analysis identified cytokeratin 10 (K10) as a candidate autoantigen in RP. Monoclonal anti-K10 antibodies reproduced patterns of ischemic tissue loss and endothelial cell apoptosis; K10 knockout or depletion of anti-K10 activity in serum was protective. Cold exposure enhanced K10 expression and in vivo tissue loss. Conclusion: Anti-K10 antibodies are sufficient to mediate RP-like ischemia in murine models and are implicated in the pathogenesis of RP in patients with anti-RNP autoimmunity.
Original language | English (US) |
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Pages (from-to) | 1489-1499 |
Number of pages | 11 |
Journal | Arthritis and Rheumatology |
Volume | 70 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2018 |
ASJC Scopus subject areas
- Immunology and Allergy
- Rheumatology
- Immunology