Rituximab, anti-CD20, induces in vivo cytokine release but does not impair ex vivo T-cell responses.
Pre-formed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong transplant waiting time. We hypothesized that rituximab (RIT) could reduce PRA via B-cell depletion. As part of a Phase I study of single RIT dose, we studied in vivo and ex vivo effects on T-cell immune responses. Nine subjects (n = 3) were treated at 50, 150, and 375 mg/m(2). Serum interleukin-1alpha (IL-1alpha), IL-6, IL-12, tumor necrosis factor beta (TNF-beta), and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay (ELISA). T-cell function was monitored with T-cell proliferation assays. IL-6 levels rose in eight patients (7.15 +/- 4.38 pg/mL to 86.22 +/- 77.08, p = 0.021). The high-dose group had detectable TNF-betapost rituximab infusion (874.7 +/- 1466.5 pg/mL). There was no decline in T-cell proliferation in response to phytohemagglutinin or allogeneic lymphocyte stimuli. Stimulation indices in the presence of both concentrations of tetanus toxoid rose significantly at 4 weeks.
Department of Surgery, Indiana University, Indianapolis, IN, USA.
Avinash
A
Agarwal
Carlos A
CA
Vieira
Benita K
BK
Book
Richard A
RA
Sidner
N S
NS
Fineberg
Mark D
MD
Pescovitz
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000096:biosynthesis / Q000737:chemistry*; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000378:metabolism; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013745:Tetanus Toxoid / Q000494:pharmacology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D016207:Cytokines; D007375:Interleukin-1; D010835:Phytohemagglutinins; D013745:Tetanus Toxoid; D000069283:Rituximab; D007371:Interferon-gamma