Clinical correlates of monospecific anti-PM75 and anti-PM100 antibodies in a tri-nation cohort of 1574 systemic sclerosis subjects

Abstract

Objective: Autoantibodies directed against the two principal antigens of the human exosome complex, PM75 and PM100, are present in systemic sclerosis (SSc) sera and have been associated with myositis and calcinosis. However, there is a paucity of data on the clinical correlates of these autoantibodies separately and in the absence of other SSc-specific antibodies. The aim of this study was to assess the clinical correlates of monospecific anti-PM75 and anti-PM100 in SSc. Methods: A tri-nation cohort of 1574 SSc subjects was formed, clinical variables were harmonized and sera were tested for anti-PM75 and anti-PM100 antibodies using a line immunoassay. Results: Forty-eight (3.0%) subjects had antibodies against PM75 and 18 (1.1%) against PM100. However, only 16 (1%) had monospecific anti-PM75 antibodies and 11 (0.7%) monospecific anti-PM100 antibodies (i.e. in isolation of each other and other SSc-specific antibodies). Monospecific profiles of each autoantibody included more calcinosis. An increased frequency of myositis was only seen in subjects positive for both anti-PM75 and anti-PM100 antibodies. Lung disease was only associated with anti-PM75 and subjects with anti-PM100 antibodies had better survival compared to other antibody subsets. Conclusion: The prevalence of monospecific anti-PM75 and anti-PM100 antibodies in this large SSc cohort was low. Disease features associated with anti-PM/Scl antibodies may depend on particular and possibly multiple antigen specificities. However, due to the small samples, these results need to be interpreted with caution. International collaborations are key to understanding the clinical correlates of uncommon serological profiles in SSc.

• Autoantibodies
• anti-PM/Scl antibodies
• autoimmunity
• observational cohort
• systemic sclerosis

Declaration of interest

The authors report no conflicts of interest.

The CSRG received funds and/or gifts in kind from the Canadian Institutes of Health Research (CIHR) (grant #FRN 83518), the Scleroderma Society of Canada and its provincial Chapters, Scleroderma Society of Ontario, Sclérodermie Québec, Cure Scleroderma Foundation, INOVA Diagnostics Inc. (San Diego, CA, USA), Euroimmun (Lubeck, Germany), Fonds de la recherche en santé du Québec (FRSQ), the Canadian Arthritis Network (CAN), the Arthritis Society Research Chair (University of Calgary) and the Lady Davis Institute of Medical Research of the Jewish General Hospital, Montreal, QC. The CSRG has also received educational grants from Pfizer and Actelion pharmaceuticals. Dr. Hudson is funded by the Fonds de la recherche en Santé du Québec. Dr. Nikpour holds an NHMRC research fellowship (APP1071735). ASIG receives unrestricted grants from Actelion, Pfizer and GSK, and is also supported by Scleroderma Australia. Dr. Assassi is funded by the NIH/NIAMS K23AR061436. Dr. Mayes is funded by NIH/NIAMS AR055258. The GENISOS cohort receives funding from DoDW81XWH-13-1-0452. The funding sources had no role in the design of the study, analysis of the data, preparation of the manuscript and decision to submit for publication.

Supplementary material available online

Supplementary Table 1