Background/Purpose: Myopathy is an important cause of morbidity in systemic sclerosis (SSc).  Nevertheless, scleromyositis remains incompletely characterized owing at least in part to its clinical heterogeneity. Sub-classifying patients with either SSc or autoimmune inflammatory myositis (AIM) by autoantibody profiles is a useful way of identifying more homogeneous subsets. We hypothesized that grouping patients with scleromyositis based on their autoantibody profile would also allow us to identify distinct clinical phenotypes.

Methods: Thirty-six subjects from a referral centre were identified as having a concomitant diagnosis of SSc and AIM by two rheumatologists. A retrospective chart review was performed and data on demographics, clinical features, laboratory tests and other relevant investigations were extracted.  Autoantibodies were assessed by indirect immunofluorescence (IIF) on Hep-2 substrates and line immunoassay (LIA, myositis and systemic sclerosis profiles: Euroimmun, Lübeck, Germany). Subjects were divided into 3 groups based on their autoantibody profiles: group 1 included subjects with SSc-specific autoantibodies (anti-centromere, -topoisomerase 1, -RNA polymerase III, -Th/To, -fibrillarin), group 2 with SSc-overlap autoantibodies (anti-PM/Scl, -U1RNP, -Ku), and group 3 without any fine specificities (hereinafter referred to as ‘seronegative’).

Results: Of the 36 subjects with scleromyositis, 8 (22%) had SSc-specific autoantibodies, 11 (31%) had SSc-overlap autoantibodies and 17 (47%) were seronegative on LIA (Table 1). However, 14 (82%) of the seronegative subjects had positive IIF staining: 6 nuclear speckled and cytoplasmic; 5 nuclear speckled; 2 cytoplasmic; and 1 nucleolar. Most of the subjects were women (83%), had Raynaud’s phenomenon (92%), and abnormal nailfold capillaroscopies (79%). One third of the scleromyositis subjects had no skin involvement and the absence of skin disease was seen more frequently in SSc-overlap and seronegative subjects. Subjects with SSc-specific autoantibodies had lower median creatine kinase (CK) levels (290 IU/L (48-1344)). Subjects with SSc-overlap autoantibodies presented a more classical pattern of weakness associated with significant CK elevation (median (range) 2860 IU/L (159-5075)). Distal weakness was a major feature of seronegative subjects (65%) and head drop was found more frequently in both SSc-associated (38%) and seronegative individuals (29%).

Conclusion: In this carefully phenotyped cohort, autoantibody profiles identified three subsets of scleromyositis associated with distinct patterns of muscle involvement. Just under 50% of subjects had no SSc- or myositis-specific autoantibody identified by LIA, although most of these had positive IIF. Studies are underway to correlate these results with muscle histopathology and to identify novel autoantibodies associated with scleromyositis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibody-profiles-delineate-three-distinct-subsets-of-scleromyositis/