RESEARCH - Remicade, but not Enbrel, induces IgM anti-dsDNA as main antinuclear reactivity

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Arthritis Rheum. 2005 Jul;52(7):2192-201.

Infliximab, but not etanercept, induces IgM anti-double-stranded DNA

autoantibodies as main antinuclear reactivity: biologic and clinical

implications in autoimmune arthritis.

De Rycke L, Baeten D, Kruithof E, Van den Bosch F, Veys EM, De Keyser F.

Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.

Leen.DeRycke@...

OBJECTIVE: To analyze the clinical and biologic correlates of autoantibody

induction during longer-term tumor necrosis factor alpha (TNFalpha) blockade

with either the monoclonal antibody infliximab or the soluble receptor

etanercept. METHODS: Thirty-four patients with spondylarthropathy (SpA) and

59 patients with rheumatoid arthritis (RA) were treated with infliximab for

2 years. Additionally, 20 patients with SpA were treated with etanercept for

1 year. Sera were blindly analyzed for antinuclear antibodies (ANAs),

anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear

antigen (anti-ENA) antibodies, and antihistone, anti-nucleosome, and

anticardiolipin antibodies (aCL). The anti-dsDNA antibodies were isotyped.

RESULTS: High numbers of infliximab-treated patients with SpA or RA had

newly induced ANAs (61.8% and 40.7%, respectively) and anti-dsDNA antibodies

(70.6% and 49.2%, respectively) after 1 year, but no further increase

between year 1 and year 2 was observed. In contrast, induction of ANAs and

anti-dsDNA antibodies was observed only occasionally in the

etanercept-treated patients with SpA (10% of patients each). Isotyping

revealed almost exclusively IgM or IgM/IgA anti-dsDNA antibodies, which

disappeared upon interruption of treatment. Neither infliximab nor

etanercept induced other lupus-related reactivities such as anti-ENA

antibodies, antihistone antibodies, or anti-nucleosome antibodies, and no

clinically relevant lupus-like symptoms were observed. Similarly, infliximab

but not etanercept selectively increased IgM but not IgG aCL titers.

CONCLUSION: The prominent ANA and anti-dsDNA autoantibody response is not a

pure class effect of TNFalpha blockers, is largely restricted to short-term

IgM responses, and is not associated with other serologic or clinical signs

of lupus. Similar findings with aCL suggest that modulation of humoral

immunity may be a more general feature of infliximab treatment.

PMID: 15986349

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5986349 & dopt=Abstract

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