Background Despite inclusion in systemic lupus erythematosus (SLE) disease activity indices and classification criteria, the relationship between hypocomplementemia, disease manifestations and cumulative organ damage has not been systematically investigated. It is also unknown whether there is a particular disease phenotype associated with chronic, unresolving hypocomplementemia.
Objectives To evaluate SLE patients with a history of hypocomplementemia, to establish the relationship between clinical manifestations and organ damage. To compare low C3 to low C4 and establish relative importance for manifestations and damage parameters. To assess SLE patients with persistent hypocomplementemia to ascertain whether these patients have unique clinical characteristics.
Methods As part of a lupus cohort, C3 and C4 were measured quarterly. Using univariate and multivariate methods, those with and without a history of low C3, low C4 and both were compared and an odds ratio calculated and compared using generalized linear hypothesis testing. We then considered those who had persistent hypocomplementemia (i.e. complement never normalized, on a minimum of 3 evaluations) and compared them to patients with a similar number of assessments.
Results 2399 patients were included in the analysis; 47% had a history of low C4 and low C3 in 55%. Persistently low C3 was found in 83 (4.0%) and C4 in 65 (3.2%). A history of low C3 associated strongly with nephritis and with renal damage parameters. Low C4, in isolation, associated only with false positive RPR and the presence of arthritis. With unresolving hypocomplementemia (Table 1), strong associations were demonstrated between low C3, low C4 and both in combination and hematologic, serologic and antiphospholipid-related parameters. No associations were found for cutaneous disease. Persistently low C3 associated with nephritis.
Conclusions A history of, and chronically low C3 associates uniquely with renal disease whilst a history of low C4, associated only with arthritis and a false positive RPR.
Persistent hypocomplementemia associated strongly with other hematological and serological abnormalities. While a history of low C4 was not strongly associated with other disease activity parameters, chronically low C4 appears to be a more important marker.
Disclosure of Interest None declared