Rituximab, anti-CD20, induces in vivo cytokine release but does not impair ex vivo T-cell responses

Abstract

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/m2, Serum interleukin-1α (IL-1α), IL-6, IL-12, tumor necrosis factor beta (TNF-β), and interferon-gamma (IFN-γ) 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-β post 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.