Suppression of in vitro IgM rheumatoid factor production by diphtheria toxin interleukin 2 recombinant fusion protein (DAB 486IL-2) in patients with refractory rheumatoid arthritis.
OBJECTIVE
To investigate the effect of diphtheria toxin interleukin 2 recombinant fusion protein (DAB 486IL-2) on in vitro synthesis of immunoglobulin and rheumatoid factor (RF) in patients with severe refractory rheumatoid arthritis (RA) enrolled in a phase II, double blind, placebo controlled study.


METHODS
Anticoagulated venous blood samples were obtained before (Day 1) and after (Day 28) intravenous infusion of either DAB 486IL-2 at 0.075 mg/kg/day (12 patients) or saline placebo (10 patients) on Days 1-5. Peripheral blood leukocytes (PBL) were prepared by density gradient centrifugation, cultured in the presence and absence of pokeweed mitogen (PWM) for one week, and culture supernatants assayed for immunoglobulins and IgM RF by ELISA.


RESULTS
Compared to placebo treated patients, PWM induced IgM RF synthesis by PBL decreased after treatment with DAB 486IL-2 (p = 0.043). However, there was no apparent correlation with clinical improvement. PWM induced IgM, IgA, and IgG synthesis also tended to decrease, although the changes did not attain statistical significance. In contrast, PWM induced IgM RF, IgM, IgA, and IgG synthesis by PBL from patients treated with placebo tended to increase during the observation period. Spontaneous immunoglobulin and IgM RF production by PBL from either the DAB 486IL-2 or placebo patients remained stable.


CONCLUSIONS
These observations raise the possibility that DAB 486IL-2 may diminish B cell function either directly or indirectly through effects on T cell function, but the change may not correspond to clinical response.
Schrohenloher
R E
RE
Department of Medicine, University of Alabama at Birmingham 35294-7201, USA.
Koopman
W J
WJ
Woodworth
T G
TG
Moreland
L W
LW
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018929:Cell Culture Techniques; D004167:Diphtheria Toxin / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000187:drug effects; D007376:Interleukin-2 / Q000737:chemistry; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012217:Rheumatoid Factor / Q000096:biosynthesis* / Q000187:drug effects
D004167:Diphtheria Toxin; D007136:Immunoglobulins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D012217:Rheumatoid Factor