Abstract

Complement is known to play a key role in MS and recent work utilising proteomic analysis identified raised serum levels of C4a in patients compared to controls which decreased following relapse. In order to replicate and validate this finding which has significant implications for the pathogenesis of MS, we have measured serum C4 and C4a in 107 patients with representation from all disease subgroups and 40 controls. We also examined serial samples on 43 patients following relapse to assess dynamic changes. C4 levels showed good correlation with C4a (r=0.27, p=0.001). C4 levels were raised in MS patients (mean 267 mg/l, SD 116) compared to controls (mean 248 mg/l, SD 79; p<0.001) with no discrimination between disease subgroups. C4a levels were not significantly raised in primary (mean 1.40 mg/l, SD 0.67; p=0.89) or secondary (mean 1.69 mg/l, SD 0.70; p=0.18) progressive patients or relapsing remitting patients in remission (mean 1.39 mg/l, SD 0.79; p=0.91) compared to controls; but were significantly increased in patients in acute relapse (mean 2.07 mg/l, SD 1.07; p<0.001) and decreased significantly after 2 months (mean 1.85 mg/l, SD 0.91; p=0.028). In summary, we were able to confirm dynamic changes in C4a levels in patients in acute relapse implying a systemic humoural inflammatory component at relapse ignition; however, because of low sensitivity/specificity between patient groups it is unlikely that C4 or C4a could be employed as reliable clinical diagnostic or disease state biomarkers.