Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus?
OBJECTIVE
To examine autoantibody clusters and their associations with clinical features and organ damage accrual in patients with systemic lupus erythematosus (SLE).


METHODS
The study group comprised 1,357 consecutive patients with SLE who were recruited to participate in a prospective longitudinal cohort study. In the cohort, 92.6% of the patients were women, the mean +/- SD age of the patients was 41.3 +/- 12.7 years, 55.9% were Caucasian, 39.1% were African American, and 5% were Asian. Seven autoantibodies (anti-double-stranded DNA [anti-dsDNA], anti-Sm, anti-Ro, anti-La, anti-RNP, lupus anticoagulant (LAC), and anticardiolipin antibody [aCL]) were selected for cluster analysis using the K-means cluster analysis procedure.


RESULTS
Three distinct autoantibody clusters were identified: cluster 1 (anti-Sm and anti-RNP), cluster 2 (anti-dsDNA, anti-Ro, and anti-La), and cluster 3 (anti-dsDNA, LAC, and aCL). Patients in cluster 1 (n = 451), when compared with patients in clusters 2 (n = 470) and 3 (n = 436), had the lowest incidence of proteinuria (39.7%), anemia (52.8%), lymphopenia (33.9%), and thrombocytopenia (13.7%). The incidence of nephrotic syndrome and leukopenia was also lower in cluster 1 than in cluster 2. Cluster 2 had the highest female-to-male ratio (22:1) and the greatest proportion of Asian patients. Among the 3 clusters, cluster 2 had significantly more patients presenting with secondary Sjögren's syndrome (15.7%). Cluster 3, when compared with the other 2 clusters, consisted of more Caucasian and fewer African American patients and was characterized by the highest incidence of arterial thrombosis (17.4%), venous thrombosis (25.7%), and livedo reticularis (31.4%). By using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the greatest frequency of nephrotic syndrome (8.9%) was observed in patients in cluster 2, whereas cluster 3 patients had the highest percentage of damage due to cerebrovascular accident (12.8%) and venous thrombosis (7.8%). Osteoporotic fracture (11.9%) was also more common in cluster 3 than in cluster 2.


CONCLUSIONS
Autoantibody clustering is a valuable tool to differentiate between various subsets of SLE, allowing prediction of subsequent clinical course and organ damage.
To
C H
CH
division of Rhumatology, Johns Hopkins University, Baltimore, Maryland 21205, USA. toch@hkstar.com
Petri
M
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D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D016000:Cluster Analysis; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012261:Ribonucleoproteins / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D055517:snRNP Core Proteins; D000097585:SS-B Antigen
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D004247:DNA; D016682:Lupus Coagulation Inhibitor; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000097585:SS-B Antigen; C035356:SS-A antibodies