Autoantibodies to nuclear, cytoplasmic, and cytoskeletal antigens in renal allograft rejection.
Autoantibodies (AA) detected by indirect immunofluorescence on HEp-2 cells and lymphocyte panel reactive antibodies (PRA) were measured pretransplant and within 2 weeks after transplant nephrectomy in a group of 21 consecutive renal allograft recipients with irreversible graft rejection. No patient had clinical evidence or history of autoimmune disease. Although 43% of patients had AA and 29% had a positive PRA pretransplant, 90% had AA and 100% had a positive PRA post-transplant nephrectomy (P less than 0.0032, 0.00001, respectively). Analysis of AA detected following graft failure revealed that all were of IgG class, and more than half the patients had multiple patterns including speckled nuclear, cytoplasmic, perinuclear, mitotic spindle apparatus, and smooth muscle staining. Of 11 patients retested up to one year later, all showed a persistence of previously detected AA in both pattern and titer, although none of the patients had any other signs or symptoms of autoimmune disease. A control group of 21 transplant recipients with functioning grafts was similarly tested revealing that 35% had AA and 29% had positive PRA pretransplant, but only 14% had AA and 14% positive PRA posttransplant. The presence of post-transplant AA or PRA was not associated with antecedent delayed graft function (ATN), rejection episodes, treatment with antithymocyte globulin, the interval posttransplantation, or subsequent graft outcome. However, pretransplant AA and PRA in both groups were associated with prior graft loss, but not with other variables examined. These findings indicate that serologically detectable sensitization to lymphocyte (HLA) antigens and the presence of persistent, multiple autoantibodies to nuclear, cytoplasmic, and cytoskeletal antigens is a frequent occurrence following graft loss. Furthermore, the development of AA following graft rejection appears to be unrelated to the prior presence or subsequent development of clinical autoimmune disease.
D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology*; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens; D006801:Humans; D007074:Immunoglobulin G; D007425:Intracellular Membranes / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D008566:Membranes / Q000276:immunology*; D008875:Middle Aged; D009130:Muscle, Smooth / Q000276:immunology; D009392:Nephrectomy
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies