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 after marrow transplantation mimic normal ontogeny. The early B-cell repertoire during ontogeny is characterized by a high degree of autoreactivity and interconnectivity. Therefore, in a prospective analysis, 95 consecutive recipients of an allogeneic marrow transplant were screened for the occurrence of various autoantibodies and 47 of these 95 were also screened for monoclonal gammopathies. None of the patients developed antibodies specific for systemic autoimmune disorders. In contrast, a high prevalence of natural antibodies (79/95) was found early post-transplant, with 58 of these 79 patients developing two or more autoantibodies. According to multiple regression, the mean number of natural antibodies (95% confidence limits in parentheses) depends significantly (P = 0.006) on the status of CMV infection: 0.9 (0.4; 1.6) CMV-negative: 2.0 (1.0; 3.3) asymptomatic CMV infection; 3.1 (1.7; 5.0) CMV disease. Sex, age, underlying disease, conditioning therapy, acute graft-versus-host disease and CMV serology of donor and recipient pretransplant did not affect the number of natural autoantibodies. Monoclonal gammopathies were detected in 12/47 patients with a predominance of the IgG-kappa subtype. All these 12 patients suffered from a viral infection (CMV, n = 11: influenza strain A, n = 1). The high degree of self-reactivity post-transplant further supports the hypothesis that B-cell reconstitution mimics ontogeny. Moreover, these data indicate nonspecific polyclonal, CMV-mediated, presumably T-cell independent B-cell stimulation and disturbed T-cell regulatory function following allogeneic BMT.
Hebart
H
H
Medizinische Klinik und Poliklinik, Universität Tübingen, Germany.
Einsele
H
H
Klein
R
R
Fischer
I
I
Bühler
S
S
Dietz
K
K
Jahn
G
G
Berg
P A
PA
Kanz
L
L
Müller
C A
CA
D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology*; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D007146:Immunoglobulin lambda-Chains / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000276:immunology / Q000821:virology*; D012189:Retrospective Studies; D014181:Transplantation Immunology
D018941:Antigens, CD19; D001323:Autoantibodies; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains