Regulation of plasma complement C4 and factor b levels in murine systemic lupus erythematosus

We have investigated plasma concentrations of complement C4 and Factor B in three murine models of systemic lupus erythematosus, MRL-lpr/lpr (H-2k), BXSB (H-2b) and NZB/W (H-2d/z) mice. Levels of C4 and Factor B were also determined in the following control strains: C57BL/6 (H-2b), BALB/c (H-2d) and MRL-+/+ (H-2k). Although complement levels varied independent of disease activity, strain-dependent and intra-strain gender-dependent differences, were detected. Male BXSB mice exhibited significantly lower C4 levels than male C57BL/6 mice from 2.5-5.5 months of age but Factor B levels were not significantly different. Female BXSB, which do not exhibit early disease, had Factor B and C4 levels very similar to C57BL/6 mice. Male and female MRL-lpr/lpr mice, with active disease, had levels of C4 and Factor B which were not significantly different from those in age matched MRL-+/+ mice. While not significantly different from control, several female MRL-lpr/lpr mice with active disease had elevated C4 levels and normal Factor B levels. Male NZB/W, without disease, exhibited an age-dependent decline in plasma C4 but no decline in Factor B levels. In contrast, NZB/W females, with evidence of disease, exhibited age-dependent increases in C4 and Factor B. Interestingly, some animals with elevated C4 had normal Factor B levels and vice-versa. These observations suggest that complement levels do not necessarily reflect disease activity or morbidity patterns in murine lupus and therefore suggest caution in the interpretation of complement levels in the human counterpart of the disease.