Clinical correlations of serum anti-dsDNA immunoglobulin subfamilies in patients with systemic lupus erythematosus (SLE)

Systemic lupus erythematosus (SLE) is an extremely heterogenous autoimmune disorder. A key biomarker, the double stranded (ds) DNA autoantibody, provides diagnostic specificity for SLE. We analyzed anti-dsDNA by mass spectrometry (MS) to determine if ascertaining the autoantibody's heavy chain variable region (IGHV) may hold any clinical relevance. A cross-sectional study of 32 SLE patients (75% female) in a single center was performed. Serum anti-dsDNA was subjected to MS analyses. Obtained IGHV subfamilies were correlated with active clinical features of SLE, as determined by medical record reviews. We established significant associations with the presence of IGHV3-15 and active neuropsychiatric lupus (relative risk [RR] 5.71); IGHV3-21, IGHV3-23 and IGHV4-34 and leukopenia (RR 13.70, 2.14 and 10.29 respectively); and IGHV3-23 and serositis (RR 2.41) and cutaneous lesions (RR 2.82). This study provides the first evidence for the clinical benefits of deep anti-dsDNA profiling through MS, and provides an avenue for improving predictive medicine for SLE patients. Future studies with a greater number of patients, and to determine if these subfamilies have direct pathogenic properties are required.