Clinical value of simultaneous detection of anti-dsDNA and anti-chromatin antibodies using a multiplex immunoassay in systemic lupus erythematosus: a 5-year retrospective study

OBJECTIVE: To assess the clinical relevance of concurrent measurement of anti-chromatin antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies using a multiplex immunoassay in systemic lupus erythematosus (SLE), focusing on their association with organ-specific manifestations and disease activity. METHODS: Adult patients diagnosed with SLE based on the 2012 Systemic Lupus International Collaborating Clinics or 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology criteria and followed in our university hospital between 2015 and 2019 were retrospectively included if they had at least one positive detection of anti-dsDNA and/or anti-chromatin result by a multiplex immunoassay, with clinical data available within the 30 days before or after testing. Clinical manifestations, treatments, laboratory parameters and disease activity (SLE Disease Activity Index 2000 (SLEDAI-2K)) were compared using mixed models and correlation coefficients. RESULTS: 98 patients (88% women; median age 42 (IQR: 35-50)) had 677 antibody evaluations. Levels of anti-dsDNA and anti-chromatin antibodies were correlated (r=0.39, 95% CI 0.21 to 0.55). Results were discordant in 59 patients (60%), representing 215 assessments (32%), with anti-chromatin antibodies being detected without anti-dsDNA in 111/677 samples (16%). Rise in anti-dsDNA antibody titre was associated with cutaneous (OR 2.29, 95% CI 1.43 to 3.68) and musculoskeletal involvement (OR 1.29, 95% CI 1.02 to 1.64), while anti-chromatin antibody increase was linked to neuropsychiatric manifestations (OR 1.54, 95% CI 1.03 to 2.29). The increase of either antibody titre was independently associated with proteinuria >0.5 g/24 hours (anti-dsDNA antibody: OR 1.17, 95% CI 1.11 to 2.74; anti-chromatin antibody: OR 1.71, 95% CI 1.02 to 2.87). Correlation with SLEDAI-2K was moderate for anti-dsDNA (r=0.55; 95% CI 0.39 to 0.67), and weaker for anti-chromatin (r=0.32; 95% CI 0.16 to 0.51]). CONCLUSIONS: Concomitant measurement of anti-dsDNA and anti-chromatin antibodies using a multiplex immunoassay system brings complementary information for diagnosis and monitoring of SLE. Both antibodies are associated with disease activity and renal involvement, while anti-chromatin antibodies are associated with neuropsychiatric flares. Anti-chromatin antibodies provide additional diagnostic value, particularly in the absence of anti-dsDNA positivity that was observed in 16% of our cohort.