title: Severe hypogammaglobulinemia persisting for 6 years after treatment with rituximab combined chemotherapy due to arrest of B lymphocyte differentiation together with alteration of T lymphocyte homeostasis.
abstract: We report a case of prolonged severe hypogammaglobulinemia after rituximab combined chemotherapy for follicular lymphoma. Although the patient's globulin level was within the normal limits before treatment, the level of IgG dropped below 100 mg/dL, and both IgA and IgM became undetectable after treatment, and the levels have shown no changes for 6 years despite recovery of peripheral B cell counts. Phenotypic analysis of B cells revealed a reduction of class-switched CD27+IgM-IgD- memory B cells below 0.5% and overexpression of CD95. On the other hand, we observed the predominance of memory T cell subsets in both of CD4+ and CD8+ T cells as the result of reduction of naïve T cells. These increased memory T cells overexpressed activation markers such as CD69, CD95, and HLA-DR. Furthermore, the patient's B cells failed to differentiate into memory B or plasma cells in the presence of IL-6, IL-10, IL-15, and BAFF in vitro in comparison with those from healthy controls and showed significant impairment of IgG production. These findings suggest that rituximab combined chemotherapy may induce persistent differentiation arrest and apoptosis of B cell lineage with alteration of T lymphocyte homeostasis resulting in pan-hypogammaglobulinemia.
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Irie
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shirota
authors.forename: Chihiro
authors.initials: C
authors.lastname: Suzuki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tajima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Kameoka
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ishii
mesh_terms: D000361:Agammaglobulinemia / Q000188:drug therapy* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D011344:Procarbazine; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone