Association of anti-PM/Scl antibody with risk of malignancy in scleroderma.

C. Bruni¹, A. Lages², H. Patel³, J. Harvey³, V. Ong⁴, M. Matucci-Cerinic¹, E. Derrett-Smith⁴, C.P. Denton⁴

1 Department of Rheumatology, AOU Careggi, Firenze (Italy)

2 Affiliation servicio de Medicina Interna, Hospital De Braga, Braga (Portugal)

3 Department of Clinical Immunology, Royal Free Hospital, London (UK)

4 Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Campus, London (UK)

Background/Purpose: Anti-PM/Scl antibodies are heterogeneous autoantibodies in scleroderma (SSc) directed mainly against 75kDa and 100kDa 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. In this study, we characterised the clinical and detailed serological phenotype of anti-PM/Scl positive SSc patients from a single centre cohort of 2200 patients and identified 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. 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, gastrointestinal and muscle involvement 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 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.

Conclusion: 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.

Table 1. Prevalence of clinical, instrumental and laboratory features in the study population
	Total PM-Scl population (n=70, 100%)		PM-Scl Patients with Cancer (n=13, 18.6%)		Cancer VS non cancer population – p value
Median Age	58.4 ± 14.0		60.9 ± 10,3		0.566
Female Sex	56	80.0%	9	69.2%	0.277
Median Age at SSc onset	44.1 ± 14.5		46.5 ± 9.9		0.365
Age at Cancer onset ± SD			55,2 ± 11.7		N.A.
Smoking history	32	45.7%	7	53.8%	0.486
LcSSc	47	67.1%	10	76.9%	0.740
DcSSc	20	28.6%	3	23.1%
mRSS	4	(2-43)	11	(2-34)	0.204
Digital Ulcers	14	20.0%	5	38.5%	0.119
Calcinosis	27	38.6%	5	38.5%	>0.99
Gastrointestinal involvement	44	62.9%	9	69.2%	0.756
Pulmonary Hypertension	7	10.0%	2	15.4%	0.611
Myositis Overlap	43	61.4%	7	53.8%	0.545
Lung involvement	40	57.1%	7	53.8%	>0.99
Articular involvement	27	38.6%	2	15.4%	0.067
Renal involvement	4	5.7%	1	7.7%	0.569

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