Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus?

Abstract

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-doublestranded 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.Conclusion. Autoantibody clustering is a valuable tool to differentiate between various subsets of SLE, allowing prediction of subsequent clinical course and organ damage.

Cluster Analysis of an Array of Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus

“…In the second cluster analysis, after inclusion of aPL, we identified 4 separate clusters of autoantibodies (Table 1). Three clusters identified in our analysis were similar to autoantibody profiles previously described in patients with SLE by To and Petri 9 . In our analysis we additionally identified a cluster characterized by the absence of specific autoantibodies.…”

Prophylactic Anticoagulation in Nephrotic Syndrome

“…1,2 Most noteworthy among these disorders are the various forms of primary and secondary nephrotic syndrome, 1,2 systemic lupus erythematosus with "lupus anticoagulant", 3 granulomatous vasculitis (Wegener's granulomatosis), 4 and Behçet syndrome. 5 In the recent past, the greatest attention to thromboembolic risk and its management has been given to the nephrotic syndrome.…”

Avaliação clínico-laboratorial de pacientes com síndrome antifosfolípide primária segundo a frequência de anticorpos antinucleares (FAN Hep-2)

“…This activation has been demonstrated by the presence of at least 30 different types of autoantibodies related to APS. 27 The higher frequency of deep venous thrombosis in ANA Hep-2 positive individuals had been demonstrated in patients with SLE; 28,29 however, studies demonstrating these findings in patients with PAPS cannot be found in the literature. It is known that SLE patients are at higher risk to develop thromboembolic phenomena and that this risk is higher when antiphospholipid antibodies are present.…”

“…It is known that SLE patients are at higher risk to develop thromboembolic phenomena and that this risk is higher when antiphospholipid antibodies are present. [28][29][30] In addition, there seems to be clusters of autoantibodies, such as a combination of aCL, antinative DNA, and LAC, that discriminate a population of SLE patients with a higher risk of thromboembolic events. [28][29][30] The present study demonstrated that approximately 1/3 of PAPS patients could be ANA Hep-2 positive and most of these individuals had titers > 1/320.…”

“…[28][29][30] In addition, there seems to be clusters of autoantibodies, such as a combination of aCL, antinative DNA, and LAC, that discriminate a population of SLE patients with a higher risk of thromboembolic events. [28][29][30] The present study demonstrated that approximately 1/3 of PAPS patients could be ANA Hep-2 positive and most of these individuals had titers > 1/320. The finding of six patients with specific antibodies, except for rheumatoid factor, at low titers and not confirmed by a more specific test, raises the possibility that these individuals might develop other connective tissue diseases.…”