Effects of multidose combination chemotherapy on the humoral immune system.
Patients receiving multidose combination chemotherapy are at risk for severe, life-threatening infections, caused by among others encapsulated bacteria like Streptococcus pneumoniae. The splenic marginal zone is essential in the initiation of immune responses to S. pneumoniae. We analyzed effects of multidose combination chemotherapy on B-cell subpopulations. Immune response capacity was evaluated by using Pneumovax (PPS) or Tetavax (TT) as antigenic challenge. Three days after finishing therapy, all B-cell subpopulations in bone marrow and spleen were severely reduced, including the mature marginal zone B-cell population. When analyzing the anti-PPS immune response capacity at 3 days after finishing therapy, we found that the IgM antibody levels did not differ significantly from control immunized rats. The IgG antibody levels were significantly lower compared to control immunized rats but still significantly higher compared to unimmunized rats. The depletion of marginal zone B cells by multidose combination chemotherapy most likely contributes to the prolonged period that patients are at risk for developing severe infections after chemotherapy, despite the capacity to generate sufficient antibody levels. It is conceivable that the local (temporary) loss of immunological memory, together with the supposed inability to generate a humoral response in a short time frame, plays an important role in this vulnerability.
Department of Pathology and Laboratory Medicine, University Hospital Groningen, NL-9700 RB Groningen, The Netherlands.
A
A
Zandvoort
M E
ME
Lodewijk
P A
PA
Klok
W
W
Timens
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D022242:Pneumococcal Vaccines / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022242:Pneumococcal Vaccines; D013745:Tetanus Toxoid; D003520:Cyclophosphamide; D002945:Cisplatin