Immunogenetic prediction of pulmonary fibrosis in systemic sclerosis

doi:10.1016/0140-6736(91)91235-M

The Lancet

Volume 338, Issue 8768, 14 September 1991, Pages 661-662

https://doi.org/10.1016/0140-6736(91)91235-M Get rights and content

Abstract

75 systemic sclerosis patients were independently tested for pulmonary fibrosis, autoantibodies, and MHC class II genes. 24 of 42 (57%) patients with pulmonary fibrosis had either HLA DR3/DRw52a or anti-Scl-70 vs 2 of 33 (6%) patients without pulmonary fibrosis. The presence of DR3/DRw52a or anti-Scl-70 gives a relative risk of 16·7 for the development of pulmonary fibrosis in a patient with scleroderma—a risk substantial enough to require careful monitoring of these patients and treatment at an early stage of disease.

References (9)

J. Bidwell
DNA-RFLP analysis and genotyping of HLA-DR and DQ antigens
Immunol Today
(1988)
Ec Leroy et al.
Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis
J Rheumatol
(1982)
Cj Lynch et al.
Histocompatibility antigens in progressive systemic sclerosis (scleroderma)
J Clin Immunol
(1982)
Vd Steen et al.
Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis
Arthritis Rheum
(1988)

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Anti-Scl70 antibodies have been associated with diffuse cutaneous form, disease activity, increased risk of pulmonary fibrosis, and worse clinical outcomes. More than 85% of Scl-70 antibody-positive SSc patients will eventually develop pulmonary fibrosis68 with a sensitivity and specificity for the prediction of ILD of 45% and 81%, respectively.69 Among anti-Scl70(+) SSc patients, African Americans present with more advanced fibrotic lung disease and worse survival compared with Caucasians.70
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SHORT REPORTSImmunogenetic prediction of pulmonary fibrosis in systemic sclerosis

Abstract

Immunol Today

Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis

J Rheumatol

Histocompatibility antigens in progressive systemic sclerosis (scleroderma)

J Clin Immunol

Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis

Arthritis Rheum

SHORT REPORTS
Immunogenetic prediction of pulmonary fibrosis in systemic sclerosis