Autoimmune mechanisms in inflammatory eye disease.

This paper summarises the principal immunopathological mechanisms which may underlie ocular inflammation and draws attention to how autoimmune reactions may be regulated by idiotypic networks of the immune system. The study of autoimmunity in inflammatory eye disease is illustrated by our current investigations of retinal vasculitis in man and of experimental autoimmune uveoretinitis in rodents where three lines of evidence indicate that immune complex formation may be a compensatory host response to the development of antiretinal autoimmunity. In discussing immunological implications of these results we suggest that retinal inflammation in antiretinal autoimmunity is limited by a protective anti-idiotypic antibody response and that retinal disease arises when this compensatory response is improperly balanced. The clinical implications of this reasoning include the identification of patients at risk of relapse of ocular disease and the development of therapeutic methods for restoring an imbalanced anti-idiotypic autoimmune response towards normality.

Cyclosporin A in the treatment of posterior uveitis.

Cyclosporin A was used in nine patients with severe refractory posterior uveitis. Four patients had Behcet's disease, one had sarcoidosis, one had HLA B27 related arthritis and uveitis and three had idiopathic retinal vasculitis. The drug had beneficial ocular effects in all patients in the early stages of treatment with an improvement in the visual acuity and reduction in the severity of inflammation. The relapse rate and need for additional steroids were reduced in all patients. However, renal function deteriorated in seven patients to such an extent that the dose of Cyclosporin A had to be reduced with consequent relapse of uveitis.

The role of circulating immune complexes in the aetiology of polymorphic eruption of pregnancy.

Circulating immune complexes were measured in 35 patients with polymorphic eruption of pregnancy employing three different techniques. No significant abnormalities were detected by the C1q solid phase binding assay and polyethylene glycol precipitation of immunoglobulin G. However, using a solid phase polyclonal rheumatoid factor binding assay, which detects small immune complexes, we demonstrated a significant reduction in the level of circulating immune complexes during the acute stage of the eruption. We suggest that the leakage of small immune complexes through dilated upper dermal vessels may play a role in the aetiology of polymorphic eruption of pregnancy.

Anti-retinal autoimmunity and circulating immune complexes in patients with retinal vasculitis.

Sera from 44 patients with isolated retinal vasculitis (RV), 38 patients with retinal vasculitis accompanying systemic inflammatory diseases (RV + SID), and 33 patients with a similar range of systemic inflammatory diseases without eye involvement (SID alone) were assayed for circulating immune complexes (CIC) and for anti-retinal autoantibodies. CIC were present in 41% of patients with isolated RV and 55% of patients with RV + SID, whilst anti-retinal antibodies were present in about 70% of all patients with RV. 42% of those with SID alone had CIC and 30% of those with SID alone had retinal autoantibodies. Titres of anti-retinal antibodies were higher in patients with RV than in those with SID alone. In isolated RV there was an inverse relation between pronounced retinal autoimmunity and the occurrence of CIC--i.e., the more severe autoimmune retinal disease occurred in CIC-negative patients. Most patients with RV + SID tended to have mild or moderate retinal disease accompanied by both retinal autoantibodies and CIC, but severe retinal disease occurred in CIC-positive patients who did not have circulating anti-retinal antibodies. Patients with SID alone had high titres of retinal antibodies only when they were CIC-positive. It is suggested that the formation of CIC, possibly of an idiotype/anti-idiotype nature, may be a compensatory mechanism accompanying anti-retinal autoimmunity and that an imbalance between autoimmunity and immune complex formation may be an important predisposing factor in the development of retinal inflammatory disease.

Autoimmunity and circulating immune complexes in retinal vasculitis.

This paper presents the results of a point-prevalence study of circulating autoantibodies and immune complexes in 44 patients with isolated retinal vasculitis (RV alone), 38 patients with retinal vasculitis accompanied by systemic inflammatory disease (RV + SID), and 33 patients with a similar range of systemic inflammatory disease but without eye involvement (SID alone). In isolated retinal vasculitis, antiretinal antibodies, non-retinal antibodies, and circulating immune complexes each showed a prevalence of about 50 per cent, but there was an inverse relationship between marked antiretinal autoimmunity and the occurrence of circulating immune complexes. In SID alone, antiretinal antibodies (ret-AB) were of lower prevalence (about 20 per cent) and occurred only in patients who had circulating immune complexes (CIC). Patients with RV + SID fell into two principal categories: (a) ret-AB with CIC, and (b) ret-AB without CIC. In isolated retinal vasculitis, the occurrence of high levels of retinal autoimmunity in the absence of circulating immune complexes was associated with the more severe retinal disease, while in those RV + SID patients who did not express autoimmunity, the more severe retinal disease was associated with the presence of circulating immune complexes. It is suggested that the formation of circulating autoimmune complexes, possibly of an idiotypic: anti-idiotypic character, may be a 'risk' mechanism for limiting retinal-specific autoimmunity, and that certain patients with severe retinal vasculitis may undercompensate or overcompensate in this way.

The role of the plasmalogen in the cross-reaction between group A streptococcus and human myocardium.

Ethanol-soluble mycardial material which reacts with anti-streptococcal sera in a number of immunological tests has been isolated and identified as ethanolamine plasmalogen. The reactions of cardiac plasmalogen with antistreptococcal sera was specific and could be inhibited by streptococcus-derived materials. Guinea-pigs sensitized to streptococci gave positive skin reactions when challenged with myocardial plasmalogen. The pattern of the immunofluorescent staining given by antiplasmalogen sera was very much like that given by antistreptococcal sera. Nevertheless, the plasmalogen failed to compete for tissue-bound myocardial antigens when tried as an inhibitor of the immunofluorescent staining of myocardium either by antistreptococcal sera or by antiplasmalogen sera. A hypothesis of the role of the plasmalogen in the formation of complexes between streptococci and myocardium-derived material in the initiation of autoimmune processes is presented.