Disease activity in systemic lupus erythematosus in relation to direct Coombs test positivity without haemolytic anaemia: a single-centre cross-sectional study

Background: The prevalence of Direct Coombs test (DCT) positivity in systemic lupus erythematosus (SLE) ranges from 12.8% to 65.2%. Approximately 5-11% of people with SLE have autoimmune haemolytic anaemia (AIHA), characterised by autoantibodies against erythrocytes that cause haemolysis. In about half of the SLE patients, DCT positivity occurs even in the absence of AIHA, likely due to immune complexes binding to red blood cells via complement receptor 1 (CR1), suggesting a higher immune complex load. Objectives: To determine the DCT positive rate in SLE patients without AIHA and its association with disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) score. Methods: This descriptive cross-sectional study was conducted at a tertiary care centre in South India from March 2023 to March 2025. SLE patients who met the 2019 ACR/EULAR classification criteria without AIHA were included. Disease activity was measured using the SLEDAI-2K. The DCT was performed using the standard antihuman globulin, and a reaction grade of 1+ or higher was considered positive. The study compared DCT-positive and DCT-negative groups using statistical analysis. Results: The study included 92 SLE patients, most of whom were female (97.8%), with a mean age of 35.1 ± 9.49 years, and a mean disease duration of 4.56 ± 4.36 years. DCT positivity without AIHA was found in 33.6% of the patients. DCT-positive patients had a higher median SLEDAI-2K score than DCT-negative patients (8 [IQR 3.5–10.5] vs 0 [IQR 0–5]; p < 0.001). DCT positivity was also strongly associated with arthritis (p < 0.001) and with higher anti-double-stranded DNA antibody levels (p = 0.008). Conclusion: In individuals with SLE, DCT positivity without AIHA was common and was associated with higher contemporaneous disease activity, arthritis, and elevated anti-double-stranded DNA antibody levels. These findings suggest that DCT positivity may reflect increased immune activity at a single point in time. However, its utility in predicting future flares or monitoring longitudinal disease activity remains uncertain and requires prospective validation.