Comparison of autoantibody specificities between traditional and bead-based assays in a large, diverse collection of patients with systemic lupus erythematosus and family members.

Diverse clinical presentations of SLE create significant diagnostic difficulties. However, the common feature of autoantibodies has been shown to associate with select clinical features (1). Previous work has found that autoantibodies are often present in SLE patient sera years before diagnosis and prior to their associated clinical symptoms (2, 3). Detection of autoantibodies contributes to SLE classification (4, 5), and some may be used to monitor the potential for disease flare (6, 7). Prevalence of autoantibodies varies among self-reported ethnic groups. Compared with European-Americans (EA), African-American (AA) SLE patients have a higher prevalence of autoantibodies targeting Sm and nRNP proteins (8–11). Autoantibody cluster analysis provides additional information about clinical symptom associations or genetic risk; however, studies to date have either relatively small patient cohorts (12–15) or use historical antibody data measured by a variety of detection methods (16). A few studies examining the prevalence of autoantibodies in blood relatives of SLE patients have shown that low levels of SLE specific autoantibodies were detectable in clinically healthy relatives (17–19). Although autoantibodies remain paramount in lupus diagnosis and management, detection of lupus specificities vary significantly between clinically available assays. To date, detailed evaluations of newer methodologies in large multi-ethnic SLE and control collections are incomplete. Historical methods of immunofluorescence and immunodiffusion autoantibody testing require specially trained laboratory personnel and are becoming less available in many US markets. Based on variability in autoantibody detection across and within select methods, it has been difficult to consistently and accurately measure prevalence of autoantibodies in diverse SLE patient cohorts. Questions remain about the number of SLE patients that would be potentially missed based upon testing of fewer autoantibody specificities with newer methodologies; the frequency of specific autoantibody detection across different races; and if healthy SLE family members would have higher rates of autoantibody specificities when using these newer methods. Our primary objective was to examine prevalence, specificity, clustering and family aggregation of specific autoantibodies within a large cohort of SLE patients, unaffected relatives, and unaffected controls. Additionally, we sought to compare anti-nuclear antibody (ANA) results between a multiplex bead assay and classical detection methods (indirect immunofluorescence and immunodiffusion) in a large multi-ethnic cohort.