CMV INFECTION AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION IS ASSOCIATED WITH THE OCCURRENCE OF VARIOUS AUTOANTIBODIES AND MONOCLONAL GAMMOPATHIES

Recent findings indicate that the kinetics of B-cell reconstitution af ter marrow transplantation mimic normal ontogeny. The early B-cell rep ertoire during ontogeny is characterized by a high degree of autoreact ivity and interconnectivity. Therefore, in a prospective analysis, 95 consecutive recipients of an allogeneic marrow transplant were screene d for the occurrence of various autoantibodies and 47 of these 95 were also screened for monoclonal gammopathies. None of the patients devel oped antibodies specific for systemic autoimmune disorders. in contras t, a high prevalence of natural antibodies (79/95) was found early pos t-transplant, with 58 of these 79 patients developing two or more auto antibodies. According to multiple regression, the mean number of natur al antibodies (95% confidence limits in parentheses) depends significa ntly (P = 0.006) on the status of CMV infection: 0.9 (0.4; 1.6) CMV-ne gative; 2.0 (1.0; 3.3) asymptomatic CMV infection; 3.1 (1.7; 5.0) CMV disease. Sex, age, underlying disease, conditioning therapy, acute gra ft-versus-host disease and CMV serology of donor and recipient pretran splant did not affect the number of natural autoantibodies. Monoclonal gammopathies were detected in 12/47 patients with a predominance of t he IgG-kappa subtype. All these 12 patients suffered from a viral infe ction (CMV n = 11; influenza strain A, n = 1). The high degree of self -reactivity post-transplant further supports the hypothesis that B-cel l reconstitution mimics ontogeny. Moreover, these data indicate nonspe cific polyclonal, CMV mediated, presumably T-cell independent B-cell s timulation and disturbed T-cell regulatory function following allogene ic BMT.