FRI0459 Association of Anti-PM/SCL Antibody with Risk of Malignancy in Scleroderma

• Published in: Annals of the rheumatic diseases Vol. 74; no. Suppl 2; p. 593
• Main Authors: Bruni, C., Lages, A., Patel, H., Harvey, J., Ong, V., Matucci Cerinic, M., Derrett-Smith, E., Denton, C.P.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2015
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2015-eular.4970

BackgroundAnti-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.ObjectivesTo 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.MethodsAnti-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.Results70 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.Table 1.Prevalence of clinical, instrumental and laboratory features in the study populationTotal PM-Scl populationPM-Scl patients with cancerCancer vs non-cancer population(n=70, 100%)(n=13, 18.6%)p valueMedian age58.4±14.060.9±10,30.566Female sex5680.0%969.2%0.277Smoking history3245.7%753.8%0.486LcSSc vs DcSSc47 vs 2067.1% vs 28,6%10 vs 376.9% vs 23,1%0.740mRSS4(2-43)11(2-34)0.204Digital ulcers1420.0%538.5%0.119Calcinosis2738.6%538.5%>0.99Gastrointestinal involvement4462.9%969.2%0.756Pulmonary hypertension710.0%215.4%0.611Myositis overlap4361.4%753.8%0.545Lung involvement4057.1%753.8%>0.99Articular involvement2738.6%215.4%0.067Renal involvement45.7%17.7%0.569 ConclusionsThe 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 InterestNone declared