Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha - Findings in open-label and randomized placebo-controlled trials
Pj. Charles et al., Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha - Findings in open-label and randomized placebo-controlled trials, ARTH RHEUM, 43(11), 2000, pp. 2383-2390
Objective, To compare the incidence of anti-double-stranded DNA (anti-dsDNA
) antibodies in rheumatoid arthritis (RA) patients receiving either single
or multiple doses of a chimeric anti-tumor necrosis factor rr (anti-TNF alp
ha) antibody or placebo infusions, with or without methotrexate, in open-la
bel, randomized, placebo-controlled trials.
Methods. Multiple sera obtained from 156 patients before and after treatmen
t with infliximab and from 37 patients treated with placebo infusions were
tested for anti-dsDNA antibodies by 3 methods: Crithidia luciliae indirect
immunofluorescence test (CLIFT), a commercial Farr assay (Ortho Diagnostics
radioimmunoassay [RIA]) in which the antigen source is mammalian DNA, and
a Farr assay employing I-125-labeled circular plasmid DNA (Central Laborato
ry of The Netherlands Red Cross Blood Transfusion Service [CLB] RIA), Patie
nts with positive findings on the CLIFT were also tested for antibodies to
histones (H1-H5) and chromatin and for IgM rheumatoid factors (IgM-RFs),
Results, None of the RA patients had a serum sample that was positive for a
nti-dsDNA antibodies by the CLIFT prior to infliximab therapy. Of the 22 pa
tients who developed a positive CLIFT result, 11 (7% of 156 exposed to infl
iximab) also had positive findings on the Ortho RIA at a concentration of >
10 units/ml and another 8 (5%) were positive at a concentration of >25 unit
s/ml. In all but 1 patient, the anti-dsDNA antibodies were solely of the Ig
M isotype, Only 1 patient had detectable anti-dsDNA antibodies by the CLB R
IA, All sera containing anti-dsDNA by the CLIFT contained antibodies to chr
omatin, and sera from 2 patients also contained antibodies to histones, IgM
-RF titers showed a significant reduction following infliximab therapy in t
hese 22 patients. One patient developed anti-dsDNA antibodies of IgG, IgA,
and IgM isotype and had positive results on both Farr assays (peaking at 22
weeks and resolving by 54 weeks); this was associated with a reversible lu
pus syndrome,
Conclusion, Anti-dsDNA antibodies of IgM class are induced by infliximab th
erapy; the frequency is dependent on the assay method used. Only 1 of the 1
56 patients who were treated with infliximab developed a self-limiting clin
ical lupus syndrome; that patient developed high titers of anti-dsDNA antib
odies of IgG, IgM, and IgA class, as detected by the CLIFT and by 2 differe
nt Parr assays.