Background Anti-PM/Scl antibodies are heterogeneous autoantibodies in scleroderma (SSc) directed mainly against 75 kDa and 100 kDa human exosome components, associated with overlap syndromes. Published data suggest that up to 12.5% of SSc patients carry this seropositivity with associations with myositis, mild skin involvement, pulmonary fibrosis, articular involvement and calcinosis and a lower prevalence of pulmonary arterial hypertension and gastrointestinal involvement.
Objectives To characterise the clinical and detailed serological phenotype of anti-PM/Scl positive SSc patients from a single centre cohort of 2200 patients and to identify a cohort within this group with increased risk of malignancy.
Methods Anti-PM/Scl positive SSc patients identified by indirect immunofluorescence pattern and confirmed on counter-immunoelectrophoresis were enrolled in the study. Sera were analyzed with line immunoassay to detect antibodies to PM/Scl 75 and PM/Scl 100. Demographics and clinical data on skin, internal organ involvement and history of malignancy were recorded.
Results 70 anti-PmScl positive patients were identified (3.1% of cohort), with frequent lung (57.1%), gastrointestinal (62.9%) and muscle involvement (61.4%) as described previously (table 1). 48 patients (68.6%) had antibodies targeting both PM/Scl 75 and 100; 6 (8.6%) PM/Scl 75 only and 16 (22.8%) PM/Scl 100 antibody only. There was a significant association between positivity for anti-PM/Scl 100 alone and malignancy (p=0.037) when compared to presence of both reactivities or reactivity to PM/Scl75 alone. 13 patients (18.6%) had developed a malignancy, 4 (30.7%) of these had onset within 36 months from SSc diagnosis and all were positive for anti-PM/Scl 100, combined with anti-PM/Scl75 in 7/13 (53.8%). The study population standardized incidence ratio (SIR) for cancer was 2.14 (CI 95%: 1.55-2.74), with higher values showed for male gender (SIR 3.10, CI 95%: 1.55-4.65) than female gender (SIR 1.95, CI 95%: 1.31-2.61). 7/13 were adenocarcinoma, mainly breast, 4/13 squamous cell and the remainder haematological malignancy.
Conclusions The association of malignancy with PM/Scl reactivity in SSc is of interest in the context of recent studies describing a potential pathogenic role of anti-RNA polymerase III antibodies with malignant disease in SSc. This cohort is otherwise representative of others in terms of demographics and clinical characteristics and underlines the importance of close surveillance for concurrent malignancy in all SSc disease subphenotypes.
Disclosure of Interest None declared