The association between heterozygous C4 deficiency and systemic lupus erythematosus (SLE) is unclear. There is a lack of data in South Asian Indians on any possible association of C4A and C4B null alleles with lupus. We aimed to study the prevalence of C4A and C4B null alleles in a cohort of SLE patients with persistently low C4 levels compared to healthy controls (HC). Patients with SLE and HC were recruited for this prospective observational study. C4 (C4AQ and C4BQ) polymorphisms were tested using a touch-down polymerase chain reaction protocol. One hundred and three SLE patients and 103 HC were included in the study. Persistently low C4 levels were observed in 25 (23.6%) of SLE. The frequency of C4A and C4B null alleles was similarly distributed across SLE and HC (4% and 3.8%, respectively). Univariate analysis showed a low age, higher proportion of elevated dsDNA, and higher positive anti-SSA (Sjogren’s syndrome-related antigen A) antibodies at presentation were associated in SLE patients with the null allele group on comparison without the null allele group. However, these associations did not persist in the multivariate analysis. In conclusion, C4 null allele frequency was similar in SLE and HC. No characteristic associations were observed in SLE with C4 null alleles was observed. Therefore, C4 null allele is an unlikely explanation for persistently low C4 in South Indian Asian patients with lupus.© 2025 John Wiley & Sons Ltd.
