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The characteristic pathogenic autoantibodies in Goodpasture's syndrome (GPS) are directed to the noncollagenous domain (NC1) of basement membrane type IV collagen. To examine whether immunization with anti-NC1 antibodies could lead to GPS-like pathology, naive BALB/c mice were immunized intradermally with a mouse IgG anti-NC1 monoclonal antibody or IgG serum fraction derived from patients with GPS. Mice immunized with normal mouse or human IgG and nonimmunized mice served as controls. Anti-NC1 antibodies of IgG isotype were detected in the sera of mice injected with anti-NC1 antibodies, but not in the sera of control mice. The presence of circulating anti-NC1 antibodies coincided in some of the mice erythrocyturia or proteinuria and pathological changes in the kidneys. No pathologic alterations were seen in the control mice. The results show that specific idiotypic manipulation can induce anti-NC1 antibodies and pathological changes resembling human GPS.

The role of the immune system in modulating atherosclerosis has recently been the subject of intensive research. Several previous authors have put forward a paradigm of the autoimmune process occurring in the vicinity of the plaque. Two recent studies have shown that immunization of rabbits with homologous modified low-density lipoprotein (LDL) led to suppression of atherosclerosis. In the current study we evaluated the effects of homologous malondialdehyde (MDA)-LDL immunizations on atherogenesis in apo-E-deficient mice. Two groups of female chow-diet-fed, apo-E-deficient mice (n = 10) were either immunized with homologous MDA-LDL or with phosphate buffer saline (PBS) at 2-week intervals. The mice were sacrificed 12 weeks following the primary immunization. The MDA-LDL-immunized mice were shown to develop high titers of anti-MDA-LDL antibodies. Atherosclerosis, determined by the lesion size at the aortic sinus, was significantly suppressed in the MDA-LDL-immunized mice as compared with their littermates immunized with PBS (mean area +/- S.D.; 74000 +/- 17300 microm2 versus 158000 +/- 12800 microm2; P0.01). No differences were found between the groups with respect to the cellular composition of the atherosclerotic plaques. The results of this study show that immunization with MDA-LDL has a protective effect in apo-E-deficient mice, and further suggests that this mouse model is suitable for studies of immunomodulation.

Objective. To examine the potential immunologic mechanism and involvement of antiphos pholipid antibodies in the pathogenesis of heart valve lesions in patients with the antiphos pholipid syndrome (APS).Methods. Immunoperoxidase and immunofluorescence staining methods were used to evaluate 13 heart valve specimens derived from eight patients with the APS, either primary or secondary to systemic lupus erythematosus. Primary antibodies to human immuno globulins, complement components, serum albumin and a monoclonal anti-idiotypic anti body to human anticardiolipin antibodies (aCL) were employed. Various tissue specimens from a patient with the APS as well as deformed and normal valves from subjects without the APS were used as controls.Results. Linear subendothelial deposition consisting of immunoglobulins with complement components but not of a non-specific serum protein was found in deformed valves from patients with the APS. None of the control valves or tissues disclosed similar deposition. The same pattern and location of staining was obtained by the anti-idiotypic antibody to aCL. A significant amount of IgG immunoglobulins that bound to cardiolipin was eluted from a valve of a patient with secondary APS.Conclusion. Deposits of immunoglobulins including aCL, and of complement components, are common in affected valves of patients with primary and secondary APS. Such deposits may be involved in the pathogenesis of valvular lesions.