Clustering analysis of anti-nuclear antibodies in systemic lupus erythematosus

Abstract

Objective To examine clusters of anti-nuclear antibodies (ANA) and their associations with clinical features in patients with systemic lupus erythematosus (SLE). Methods It was a retrospective study. 113 SLE patients were reviewed from March 2010 to May 2012 in Department of Rheumatology, Jinhua Central Hospital. ANA and specific autoantibodies to 15 kinds of nuclear antigens were tested by indirect immunofluorescence assay (IIF) and line immunoassay (LIA) respectively. Hierarchical clustering method was performed to analyze specific clusters of ANA profiles in SLE. Chi-square tests were used to investigate relationship between antibody clusters and clinical features of SLE. Results The positive rate of LIA for ANA was 97.3%,consistent with IIF method, and the total accordance rate of the both methods was 98.2%. Thirteen kinds of antigen-specific antibodies were detected in SLE patients by LIA. Clustering analysis for these antibodies showed three specific clusters in SLE, Nuc/His/dsDNA cluster (C1), low-Ro/low-La cluster (C2), and Ro/Sm/RNP cluster (C3), accounting for 36.3%, 24.8%, 38.9% of the total cases respectively. There were significant difference of AST levels among three clusters ［(32.62±21.92)U/L, (25.56±16.63)U/L, (50.41±60.86)U/L respectively for C1, C2 and C3］. High incidences of chronic cutaneous lupus, abnormal renal indicators and inflammatory synovitis were found in all three clusters. Besides, there were significant differences among three clusters for the incidences of chronic cutaneous lupus (39.0%, 39.3%, 63.6% respectively for C1, C2, C3) and leukopenia/lymphopenia (56.1%, 25.0%, 56.8% respectively for C1, C2, C3) (P<0.05). Patients in Ro/Sm/RNP cluster showed higher incidences of lupus nephritis (43.2%/26.8% or 39.3%); patients in low-Ro/low-La cluster showed low risk of hypertension (7.1%/19.5% or 22.7%); patients in Nuc/His/dsDNA cluster showed high incidences of thrombocytopenia (41.5%/21.4% or 25.0%) and high risk of lung or upper respiratory tract infection (46.3%/28.6% or 29.5%), but low incidence of neurologic symptoms (0%/3.6%% or 11.4%). Conclusion Three characterized ANA clusters are identified in SLE patients in this pilot study. Different clusters are associated with certain clinical features and complications of SLE. However, the correlations found in this study need to be investigated further in larger populations.（Chin J Lab Med,2014,37:587-592） Key words: Lupus erythematosus, systemic; Antibodies, antinuclear; Cluster analysis