Evolution of antinuclear antibodies and clinical patterns in patients with active rheumatoid arthritis with longterm infliximab therapy.
OBJECTIVE
To investigate the effect of longterm infliximab therapy on serum levels of fluorescent antinuclear and anti-double and single-stranded DNA antibodies (FANA, anti-dsDNA, anti-ssDNA) in patients with rheumatoid arthritis (RA), and their possible association with clinical evolution.


METHODS
Sera from 58 RA patients, treated for one to 3 years with infliximab, were retrospectively analyzed. Matched control groups were RA patients treated with corticosteroids or methotrexate. FANA were tested using HEp-2 cells, and anti-dsDNA and anti-ssDNA IgG by ELISA. After 28 months of infliximab therapy, clinical status was evaluated in 43/58 patients with uninterrupted therapy and associations with autoantibody levels were investigated. Data were documented for patients who discontinued infliximab.


RESULTS
Over the 3 year period, significant increases in FANA and anti-ssDNA IgG levels were observed in infliximab treated patients (p < 0.001 and p < 0.01, respectively). In 43 patients with an uninterrupted infliximab regimen, association was found between high FANA (>or= 1/1280) and lower age (p = 0.048) and patient's assessment of infliximab's efficacy (p = 0.014). Three patients developed anti-dsDNA IgG, preceded by high anti-ssDNA IgG levels, and one of them developed a lupus-like syndrome. Neither the initial presence of high FANA levels nor their increase >or= 1/1280 was significantly associated with discontinuation of infliximab. In contrast, at baseline (p = 0.0012) and at the time of infliximab discontinuation (p = 0.0078), anti-ssDNA IgG (>or= 500 arbitrary units) were more frequent in 7 patients who stopped infliximab due to skin or systemic anaphylactoid reactions.


CONCLUSIONS
Monitoring of serum FANA, anti-dsDNA, and anti-ssDNA IgG antibodies provided predictors of lupus-like symptoms and/or anaphylactoid reactions in patients with RA.
Comby
Elisabeth
E
Laboratoire d'Immunologie et Immunopathologie, UPRES-EA 2128, and Service de Rhumatologie, CHU, Caen, France. comby-e@chu-caen.fr
Tanaff
Pascale
P
Mariotte
Delphine
D
Costentin-Pignol
Valerie
V
Marcelli
Christian
C
Ballet
Jean Jacques
JJ
D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D004277:DNA, Single-Stranded / Q000276:immunology; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006304:Health Status; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D004277:DNA, Single-Stranded; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab