SUPPRESSION OF IN-VITRO IGM RHEUMATOID-FACTOR PRODUCTION BY DIPHTHERIA-TOXIN INTERLEUKIN-2 RECOMBINANT FUSION PROTEIN (DAB(486)IL-2) IN PATIENTS WITH REFRACTORY RHEUMATOID-ARTHRITIS
Re. Schrohenloher et al., SUPPRESSION OF IN-VITRO IGM RHEUMATOID-FACTOR PRODUCTION BY DIPHTHERIA-TOXIN INTERLEUKIN-2 RECOMBINANT FUSION PROTEIN (DAB(486)IL-2) IN PATIENTS WITH REFRACTORY RHEUMATOID-ARTHRITIS, Journal of rheumatology, 23(11), 1996, pp. 1845-1848
Objective. To investigate the effect of diphtheria toxin interleukin 2
recombinant fusion protein (DAB(486)IL-2) on in vitro synthesis of im
munoglobulin and rheumatoid factor (RF) in patients with severe refrac
tory rheumatoid arthritis (RA) enrolled in a phase II, double blind, p
lacebo controlled study. Methods. Anticoagulated venous blood samples
were obtained before (Day 1) and after (Day 28) intravenous infusion o
f either DAB(486)IL-2 at 0.075 mg/kg/day (12 patients) or saline place
bo (10 patients) on Days 1-5. Peripheral blood leukocytes (PBL) were p
repared by density gradient centrifugation, cultured in the presence a
nd absence of pokeweed mitogen (PWM) for one week, and culture superna
tants assayed for immunoglobulins and IgM RF by ELISA. Results. Compar
ed to placebo treated patients, PWM induced IgM RF synthesis by PBL de
creased after treatment with DAB(486)IL-2 (p=0.043). However, there wa
s no apparent correlation with clinical improvement. PWM induced IgM,
IgA, and IgG synthesis also tended to decrease, although the changes d
id not attain statistical significance. In contrast, PWM induced IgM R
F, IgM, IgA, and IgG synthesis by PBL from patients treated with place
bo tended to increase during the observation period. Spontaneous immun
oglobulin and IgM RF production by PBL from either the DAB(486)IL-2 or
placebo patients remained stable. Conclusion. These observations rais
e the possibility that DAB(486)IL-2 may diminish B cell function eithe
r directly or indirectly through effects on T cell function, but the c
hange may not correspond to clinical response. (J Rheumatol 1996;23:18
45-8)