Presence of anti-cyclic citrullinated peptide antibody isotypes in juvenile idiopathic arthritis synovial fluid indicates autoantibody production at the site of inflammation
KeywordsSynovial Fluid Juvenile Idiopathic Arthritis Juvenile Idiopathic Arthritis Patient Antibody Isotype Synovial Fluid Sample
To determine the presence and significance of anti-cyclic citrullinated (anti-CCP) antibody isotypes (IgA, IgG, IgM, and IgA/IgG) in the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients.
Anti-CCP antibody isotypes (IgA, IgG, IgM, and IgA/IgG) were assayed by enzyme-linked immunosorbent assays in the SF of 47 individual JIA patients. Patients included 28 oligoarthritis, 11 IgM RF- polyarthritis, 3 IgM RF+ polyarthritis, 3 enthesitis-related, 1 psoriatic, and 1 systemic-onset. As non-inflammatory controls, 10 patients aspirated SF with osteoarthritis (OA) were used.
Eleven of 47 (23%) JIA SF samples were positive for the different anti-CCP antibody isotypes. IgM anti-CCP antibodies were positive in 9 JIA patients, including 5 oligoarthritis, 3 IgM RF+ and 1 IgM RF- polyarthritis. IgG anti-CCP antibodies were positive in 8 JIA patients, including 4 oligoarthritis, 2 IgM RF+, 1 IgM RF- polyarthritis, and 1 enthesitis-related. Two IgM RF+ polyarthritis patients were positive for IgA anti-CCP antibodies, and also positive for all 3 isotypes. Four JIA patients were positive for 2 anti-CCP antibody isotypes, including 1 IgM RF- polyarthritis patient (IgG and IgM) and 3 oligoarthritis patients (2 IgG and IgM, 1 IgA and IgM). Five JIA patients were positive for 1 anti-CCP antibody isotype, including 3 oligoarthritis (2 IgM, 1 IgG), 1 enthesitis-related (IgG), and 1 IgM RF+ polyarthritis patient (IgM). Three JIA patients were positive for the combined IgA/IgG anti-CCP antibody ELISA, including 2 with IgM RF+ polyarthritis and 1 enthesitis-related. Polyarthritis patients demonstrated significantly higher levels of all anti-CCP antibody isotypes compared to the other JIA subtypes (p<0.05). When only evaluating the IgM RF+ polyarthritis patients against the other subtypes, the levels were even more significantly increased (p<0.05). Serum-matched IgG anti-CCP antibody data was available in 27 JIA patients and 5 healthy controls. All 3 IgM RF+ polyarthritis patients were positive for the IgG anti-CCP antibodies in serum and SF. Two JIA patients who were positive for IgG anti-CCP antibodies in SF had a negative result in serum. Date-matched SF and serum IgM and IgA data was available on 12 JIA patients. More JIA patients were positive for IgA anti-CCP antibodies in serum compared to SF, while SF showed increased positivity for IgM anti-CCP antibodies compared to serum.
While IgG anti-CCP antibodies are found in JIA patients with polyarticular disease, we found that IgM and IgG anti-CCP antibodies were detected in the SF of several subtypes of JIA. The most commonly found anti-CCP antibody isotype in JIA SF was IgM, which may partly be indicative of defective B cell class switching in these patients. IgM also plays a significant role in complement activation, indicating the significance of the complement system in JIA pathogenesis. Measurement of only IgG anti-CCP antibodies would have overlooked 4 JIA patients with elevated levels of IgA and/or IgM anti-CCP antibodies in SF, indicating the importance of measuring all 3 isotypes in SF.
Brooke E. Gilliam: None; Sandra Crespo-Pagnussat: None; Judy Ko: None; Reema H. Syed: None; Terry L. Moore: None.
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