Autoantibodies in early seropositive rheumatoid arthritis, before and during disease modifying antirheumatic drug treatment.
OBJECTIVE
Autoantibodies observed in patients with rheumatoid arthritis (RA) during clinical trials of immunomodulating agents may cause concern about possible induction of autoimmunity by the therapeutic intervention. We determined the frequency and variability of selected autoantibodies in patients with early rheumatoid factor (RF) positive RA during a prospective observational study.


METHODS
The study cohort consisted of 276 patients with active RA and with RF > or = 40 IU, who were enrolled between January 1, 1993, and April 1, 2000, before starting disease modifying antirheumatic drug (DMARD) therapy (average duration of symptoms, 7 mo). During an average of 3.5 years followup, a panel of autoantibodies was determined at entry, 6 months, 12 months, and yearly thereafter, in addition to routine clinical, radiographic, and laboratory assessments. After enrollment, patients were treated with DMARD at the discretion of their rheumatologists.


RESULTS
At entry before any DMARD therapy, antinuclear antibody (ANA; by HEp-2) values were negative in 31%, borderline (8 IU/ml) in 26%, and > 8 (mean 65.5 IU/ml) in 41%. Tender and swollen joint counts, Disease Activity Score, and RF values were significantly higher in those with ANA > 8. During followup 726 paired serial specimens were available; 12.5% changed from negative to positive ANA and 12.3% from positive to negative. Additional autoantibodies were present in specimens of 20% of the subjects; 8% had 2 and 1.4% had 3 other autoantibodies. Anti-dsDNA was detected in 13 (5.5%) patients; 4 changed from negative to positive and one from positive to negative. SSA IgG and SSB IgG autoantibodies were both present in one of these patients. Ribosomal P protein autoantibodies were noted in 2 other patients, but Sm (Smith) and uRNP/snRNP IgG autoantibodies were not present in any patient. No patient had a diagnosis of systemic lupus erythematosus. Antithyroid peroxidase (20 patients), parietal cell (15), smooth muscle (14), reticulin (9), mitochondrial (5), striational (2), SSB (2) and SCL-70 (1) autoantibodies were detected in some specimens. Seven patients were diagnosed with hypothyroidism, one with chronic thyroiditis, one with hepatitis C, and 9 with malignancies.


CONCLUSIONS
In patients with early RF positive RA the frequent occurrence of autoantibodies before and during treatment with standard DMARD may make it difficult to attribute their presence to new therapies.
Paulus
Harold E
HE
Department of Medicine, School of Public Health, University of California Los Angeles, 90095, USA.
Wiesner
Jason
J
Bulpitt
Ken J
KJ
Patnaik
Madhumita
M
Law
Jacqueline
J
Park
Grace S
GS
Wong
Weng Kee
WK
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D015331:Cohort Studies; D004247:DNA / Q000276:immunology; D004185:Disability Evaluation; D005260:Female; D006304:Health Status; D006801:Humans; D007596:Joints / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
D000974:Antibodies, Antinuclear; D018501:Antirheumatic Agents; D004247:DNA; D012217:Rheumatoid Factor