Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA.
BACKGROUND
Autoantibodies in rheumatoid arthritis (RA) are useful both for diagnosis and prognosis. Antibodies directed against citrullinated antigens have recently been shown to predict development of RA as well as poor outcome in early arthritis. Data on their role in established RA is limited. We studied the association of various autoantibodies in RA with its severity.


METHODS
A total of one hundred and twenty nine-patients with established RA was enrolled and sera were collected and stored at -70 degrees C. Data regarding erosions, deformities, and extra-articular features were collected. IgM rheumatoid factor (RF) was measured using nephelometry and value above 20 U was considered positive. IgA RF was measured by enzyme-linked immunosorbent assay (ELISA) and value above the mean+/-2 SD of normal healthy control was taken as positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP) antibodies were measured by commercial ELISA and a value above 5 U was considered as positive.


RESULTS
The prevalence of various autoantibodies was: IgM RF 82.2%, anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%. All but one patient positive for AKA were positive for anti-CCP antibodies. The presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions and deformities. None of the antibodies had any association with presence of extra-articular features. No association of IgA RF was seen with erosions, deformities, or extra-articular features. Among 23 seronegative RA patients, 11 were positive for anti-CCP antibodies and 6 were AKA positive. The presence of anti-CCP antibodies was associated with presence of deformities (p<0.05).


CONCLUSIONS
Anti-CCP antibodies are present in majority of patients with established RA including seronegative patients. Both anti-CCP and AKA, in addition to conventional marker like IgM RF, are associated with severe erosive disease.
Agrawal
Sumeet
S
Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Misra
Ramnath
R
Aggarwal
Amita
A
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000276:immunology* / Q000503:physiopathology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006304:Health Status; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007633:Keratins / Q000276:immunology; D008297:Male; D010456:Peptides, Cyclic / Q000276:immunology; D011379:Prognosis; D011859:Radiography; D012217:Rheumatoid Factor / Q000097:blood*; D012720:Severity of Illness Index
D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D007633:Keratins; D012217:Rheumatoid Factor