IL-6-anti-IL-6 autoantibody complexes with IL-6 activity in sera from some patients with systemic sclerosis

Abstract

Anti-IL-6 IgG autoantibodies, often found in sera from patients with systemic sclerosis, may increase to the level sufficient to bind significant amounts of IL-6 in serum. In our study of the role of anti-IL-6 autoantibodies in serum, we found that some sera with the autoantibodies possessed considerably higher IL-6 levels (more than 100 pg/ml) compared with most of sera without the autoantibodies. Size-exclusion HPLC of the sera with these autoantibodies demonstrated that a significant part of the serum IL-6 activity was attributable to circulating IL-6-anti-IL-6 autoantibody complexes. Gel filtration of IL-6-anti-IL-6 IgG complexes made in vitro by incubation of rIL-6 and IgG purified from the autoantibody-positive sera demonstrated that the complexes at 200 to 250 kDa were dominant ones and that IL-6 bound to the autoantibodies retained more than 60% of the original IL-6 activity. Moreover, IL-6-anti-IL-6 autoantibody complexes were shown to bind to recombinant soluble IL-6 receptors. Estimated affinity of anti-IL-6 IgG autoantibodies from two patients was fairly high (4.2 x 10(9) to 3.3 x 10(10) L/M). Therefore, the retention of IL-6 activity by IL-6-anti-IL-6 autoantibody complexes may be explained by intact receptor-binding sites on the autoantibody-bound IL-6 molecules. Taken together, these results suggest that the properties of anti-IL-6 autoantibodies are consistent with a potential role as specific carriers for IL-6 in the circulation.