Anti-IL-8 autoantibodies and complexes in rheumatoid arthritis: polyclonalactivation in chronic synovial tissue inflammation

The chemokine interleukin-8 (IL-8) is frequently associated with inflammato ry diseases, and autoantibodies against IL-8 are present in the periphery a t elevated levels in such conditions as rheumatoid arthritis (RA). Circulat ing free anti-IL-8 IgG autoantibodies correlate with inflammatory parameter s and disease severity in RA. In this study, correlations were sought betwe en these disease parameters and other antibody subclasses. We assayed IgM, IgA and IgG anti-IL-8 antibodies and IL-8 immunoglobulin immune complexes i n the serum of 29 healthy controls and 56 patients with defined RA, and com pared the results with clinical and humoral disease parameters. IgG and IgM antibodies directed against IL-8 were present in all samples. In the disea se groups, all isotypes of free anti-IL-8 antibodies correlated with increa sing humoral disease parameters like CRP and CIC and their related anti IL- 8 immune complexes. Samples which contained high titers of anti-IL-X antibo dy subclasses and complexes were RF subclass-positive, while IgM RF-negativ e sera showed low levels of anti-IL-8 and complexes. Detectable levels of I gG and IgA RF were found in all sera. Patients with extra-articular organ m anifestation showed significantly increased free IgA and IgA/IL-8 complexes , with no correlation to the IgA RF titer or IgA hypergamma-globulinemia. T he highest titers were seen in two RA cases with vasculitis and in one pati ent with colitis. Polyclonal activation of the humoral antibody system, whi ch normally precedes the resolution of an inflammatory response, can itself lead to secondary stimulation of inflammatory processes via immune complex formation. In the immune pathology of RA, it degenerates into a persistent chronic inflammation accompanied by progressive joint destruction. The pre sence of elevated IgA subclass anti-IL-8 autoantibodies in RA patients with extra-articular manifestations suggests these autoantibodies as a clinical ly useful marker of disease severity and extra-articular manifestations.