Successful immunosuppressive therapy is critical for the treatment of patients with
anti-neutrophil cytoplasmic antibody (
ANCA)-associated vasculitis and
nephrosis. However, a considerable number of patients have shown clinical resistance to
therapy.
Bacterial infection might influence the clinical response of patients to immunosuppressive drugs, but few studies have been carried out to investigate the effect of bacterial
superantigens on the efficacy of the drugs in these patients. We evaluated the suppressive efficacy of
prednisolone,
methylprednisolone,
cyclosporine, and
tacrolimus on the blastogenesis of PBMCs obtained from 12
ANCA-associated vasculitis patients (
ANCA patients), eight patients with
nephrotic syndrome, and eight healthy subjects. PBMC-stimulation index was calculated from the formula: [3H]
thymidine incorporated in the presence of stimulant (dpm)/[3H]
thymidine incorporated in the absence of stimulant (dpm). In vitro
drug concentrations giving 50% inhibition (IC50s) of PBMC blastogenesis stimulated with
concanavalin A (con A) or
toxic shock syndrome toxin 1 (TSST-1) derived from Staphylococcus aureus (S. aureus) were calculated. The IC50 values for the four drugs evaluated in TSST-1-stimulated PBMCs were significantly higher than those evaluated in con A-stimulated PBMCs in both
ANCA patients and
nephrosis patients (p<0.012-0.044). Whereas, the IC50 values for these immunosuppressive drugs, except
methylprednisolone, were not significantly different between con A- and TSST-1-stimulated PBMCs in healthy subjects. The stimulation index was not significantly different between the con A- and TSST-1-stimulated PBMCs in either of the subject groups. These observations raise the possibility that
TSST-1 induced by S. aureus
infection attenuates the clinical efficacy of
glucocorticoids and
calcineurin inhibitors in
ANCA patients and
nephrosis patients.