An Autoimmune Basis for Raynaud's Phenomenon: Murine Model and Human Disease

D. P. Ascherman, Y. Zang, I. Fernandez, E. S. Clark, W. N. Khan, L. Martinez, E. L. Greidinger

Research output: Contribution to journalArticle

2 Scopus citations

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 languageEnglish (US)
Pages (from-to)1489-1499
Number of pages11
JournalArthritis and Rheumatology
Volume70
Issue number9
DOIs
StatePublished - Sep 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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