Antibodies against PM/Scl-75 and PM/Scl-100 are independent markers for different subsets of systemic sclerosis patients

Abstract

Introduction: Anti-PM/Scl antibodies are present in sera from patients with polymyositis (PM), systemic sclerosis (SSc), and PM/SSc overlap syndromes. The prevalence of antibodies against the 75- and 100-kDa PM/Scl proteins and their clinical associations have not been studied in SSc patients in detail so far but could provide a valuable tool for risk assessment in these patients. Furthermore, it remains speculative whether commercially available test systems detecting only anti-PM/Scl-100 antibodies are sufficient in SSc patients.

Methods: Two hundred eighty sera from SSc patients, patients with other connective tissue diseases (n = 209), and healthy blood donors (n = 50) were analyzed for the presence of anti-PM/Scl-75 and anti-PM/Scl-100 antibodies by means of line immunoblot assay. For the SSc patients, possible associations between both subsets of anti-PM/Scl antibodies with clinical and laboratory findings were studied.

Results: The determination of anti-PM/Scl reactivity revealed a diagnostic sensitivity of 12.5% and a specificity of 96.9% for SSc. Among anti-PM/Scl-positive SSc patients, 10.4% and 7.1% were positive for anti-PM/Scl-75 and anti-PM/Scl-100 antibodies, respectively. The highest prevalences of reactivity to PM/Scl were detected in diffuse SSc (19.8%) and overlap syndromes (17.6%). Patients with diffuse SSc showed mainly an anti-PM/Scl-75 response, whereas most cases of overlap syndromes were characterized by reactivity to both PM/Scl antigens. The presence of anti-PM/Scl-75/100 antibodies was associated with muscular and lung involvements as well as with digital ulcers; pulmonary arterial hypertension was found less frequently. Anti-PM/Scl-75 antibodies were detected more frequently in younger and more active patients with joint contractures. Anti-PM/Scl-100 antibodies were associated with creatine kinase elevation; however, gastrointestinal involvements were observed less frequently.

Conclusions: Anti-PM/Scl antibodies are common in distinct SSc subsets and are associated with several clinical symptoms. They are directed mainly to the PM/Scl-75 antigen. Consequently, the detection of anti-PM/Scl antibodies by tests based only on PM/Scl-100 as an antigen source may miss a relevant number of SSc patients positive for these antibodies.

Figure 1

The presence of different anti-PM/Scl antibodies depends on the underlying disease subset in systemic sclerosis (SSc). Co-occurrence of antibodies that recognize different recombinant antigens as detected by line immunoblot assay in all anti-PM/Scl-positive patients (a), in patients with diffuse SSc (dSSc) (b), in patients with limited SSc (lSSc) (c), and in patients with overlap syndromes (d). anti-topo I, anti-topoisomerase I; CENP-B, centromere protein-B; PM, polymyositis.

Figure 2

Signal strengths of anti-PM/Scl-75 antibodies (a), but not of anti-PM/Scl-100 antibodies (b), depend on the underlying disease. Sera from patients with diffuse systemic sclerosis (dSSc), limited systemic sclerosis (lSSc), overlap syndromes, and undifferentiated systemic sclerosis patients were analyzed by line immunoblot assay. PM, polymyositis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SS, Sjögren syndrome; U, units; UCTD, undifferentiated connective tissue disease.