Immunologic reconstitution, autoimmunity, and T-cell immune deficiencies

A 17-month-old female with combined immunodeficiency, a proliferative response to allogeneic cells in MLC, and circulating B lymphocytes (50%, all with surface immunoglobulin M) was treated with transfer factor (TF). After six doses of transfer factor, serum levels of IgG increased from 234 mg/dl to 1071 mg/dl and a lymphocyte proliferative response was detected to pokeweed mitogen. However, no change in T-cell function was observed. Clinically, she did well, but after the eighth dose of transfer factor, she developed the nephrotic syndrome. Renal biopsy suggested immune complex glomerulonephritis. Subsequently following treatment for Pneumocystis carinii, a 20-day cultured thymus was transplanted intraperitoneally. Two weeks after thymus transplant, the patient started to develop delayed skin reactivity and in vitro mitogen responsiveness. Six weeks posttransplant, the PHA and pokeweed mitogen responses were approximately 60% of normal, but the Concanavalin A response had disappeared. Subsequently she developed a Coombs positive hemolytic anemia, a cutaneous vasculitis, and thrombocytopenia. There was no evidence of GVH disease. Multiple autoimmune manifestations developed in association with transfer factor therapy and transplantation of cultured thymus tissue. T-Cell deficiencies are predisposed to autoimmune diseases because of imbalances of regulatory T-cell function. These imbalances of regulatory T-cell function may occur especially following partial immune reconstitution. The changes in B-cell function during transfer factor therapy may have resulted from enhanced T-cell-B-cell interaction. This immunopotentiation effect of transfer factor together with partial T-cell reconstitution may have led to B-cell hyperresponsiveness and autoimmune disease.