Reactive arthritis after BCG immunotherapy: T cell analysis in peripheral blood and synovial fluid

Abstract

Objective: To investigate the pathogenic mechanism of reactive arthritis after instillation of Calmette-Guérin bacillus (BCG). Although the clinical features of reactive arthritis after BCG therapy are well described, only a few reports have studied the possible pathogenic mechanisms.

Methods: We analysed by flow cytometry the phenotype and T-cell receptor (TCR) expression of peripheral blood (PB) and synovial fluid (SF) T cells in a patient who developed reactive arthritis (ReA) following intravesical BCG immunotherapy for bladder cancer. The proliferative response of short-term T-cell lines (TCL) from PB of this patient to mycobacterial antigens was tested by bromodeoxyuridine incorporation.

Results: CD4(+) and CD8(+) SF T cells with activated and memory phenotype were observed at the onset of arthritis. We were able to detect BV-restricted expansion of CD8(+) T cells in PB (BV17) and in SF (BV5S1 and BV12). The percentage of PB and SF CD8(+) T cells that expanded diminished when the symptoms remitted. The strongest response of CD4(+) TCL from the patient in vitro was obtained for human hsp-60 in an inversely dose-dependent manner. Very important was the finding that CD8(+) TCL from the patient demonstrated no proliferative response to any antigenic challenge that was reversed after the addition of exogenous interleukin 2.

Conclusion: Although the identity of the stimulating antigen that led to the expansions observed in this patient is not clarified by the present data, both CD4(+) and CD8(+) T cells might play a role in the development of ReA following intravesical administration of BCG.