Delayed redistribution of CD27, CD40 and CD80 positive B cells and the impaired in vitro immunoglobulin production in patients with non-Hodgkin lymphoma after rituximab treatment as an adjuvant to autologous stem cell transplantation.
Recent studies have indicated that patients who received rituximab as an adjuvant to stem cell transplantation (SCT) demonstrated an increased risk of developing severe hypogammaglobulinaemia, which was found to be a result of delayed recovery of CD27 positive memory B cells and impaired isotype expression. It appears that rituximab influences both the quantity and quality of B-cell redistribution. Precisely how the B-cell repertoire regenerates after anti-CD20-mediated transient B-cell depletion in patients with non-Hodgkin lymphoma (NHL) remains to be elucidated. This study performed a phenotypical analysis of B cells in 17 NHL patients who received rituximab as an adjuvant to autologous SCT. The median period after final administration of rituximab was 36 months (range, 12-43 months). Surface antigen expression of CD27, CD40 and CD80 in NHL patients was statistically significantly different from healthy controls (n = 14). Moreover, B cells from NHL patients showed significantly impaired IgG and IgA production upon engagement of surface immunoglobulin receptors in the presence of interleukin (IL)-2, IL-10 and CD40 ligand in comparison with samples from healthy controls. The delayed recovery of memory B cells with an abnormal cell marker expression and function demonstrates that naive B cells may fail to differentiate into plasma cells, resulting in hypogammaglobulinaemia after autologous SCT and rituximab therapy.
Nishio
Mitsufumi
M
Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan. m-nishio@med.hokudai.ac.jp
Fujimoto
Katsuya
K
Yamamoto
Satoshi
S
Endo
Tomoyuki
T
Sakai
Toshiya
T
Obara
Masato
M
Kumano
Kohki
K
Yamaguchi
Keisuke
K
Takeda
Yukari
Y
Goto
Hideki
H
Sato
Norihiro
N
Koizumi
Kazuki
K
Mukai
Masaya
M
Koike
Takao
T
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D016130:Immunophenotyping; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000601:surgery / Q000628:therapy; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D019013:CD40 Antigens; D007136:Immunoglobulins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000069283:Rituximab