Evaluation of anti-citrullinated type II collagen and anti-citrullinated vimentin antibodies in patients with juvenile idiopathic arthritis

Abstract

BackgroundTo determine the prevalence and significance of anti-citrullinated vimentin and anti-citrullinated type II collagen antibodies and elucidate their role in the disease process of juvenile idiopathic arthritis (JIA).MethodsSera were obtained from 95 patients with various subtypes of JIA, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. Antibodies were measured in the sera against citrullinated and native type II collagen and vimentin (vim1-16 and vim 59-74) by enzyme-linked immunosorbent assay. Samples were compared to anti-cyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) isotypes, and our previously measured anti-citrullinated fibrinogen and α-enolase antibodies on the same patient population, in addition to erythrocyte sedimentation rate and C-reactive protein. The relationship between the anti-citrullinated antibody profile and disease activity and joint damage were also investigated.ResultsTwenty-three JIA patients (24%) demonstrated reactivity to anti-citrullinated type II collagen. Ten JIA patients (10.5%) demonstrated reactivity to anti-citrullinated vimentin 1–16 antibodies and 7 (7.4%) to anti-citrullinated vimentin 59–74 antibodies. One IgM RF-positive polyarticular patient was positive for all 5 of the citrullinated autoantibodies tested. Thirty-seven different subsets of patients were identified based on their anti-citrullinated autoantibody and RF isotype profile. No significant associations were noted with anti-citrullinated type II collagen and anti-citrullinated vimentin antibodies with joint damage or disease activity. Anti-citrullinated vimentin 59–74 antibodies demonstrated the highest overall specificity at 89.7%, with anti-citrullinated vimentin 1–16 and anti-citrullinated type II collagen antibodies at 86.2%.ConclusionThis study demonstrates that antibodies to multiple citrullinated epitopes are present in the sera of patients with various subtypes of JIA. It also demonstrates the frequent occurrence of anti-citrullinated type II collagen and anti-citrullinated fibrinogen antibodies. The presence of autoantibodies to citrullinated antigens in JIA patients is highly diverse.

Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)

“…As in adult RA, occurrence of IgM RF in JIA has been shown to correlate with joint damage or joint space narrowing [5,17,22,24-26]. Our results were in line with these studies, as we found a significant association with joint damage in the IgM RF-positive patients.…”

“…This is supported by several earlier studies showing an increased risk for radiological bone damage in patients with anti-CCP in JIA [17,22,26,28]. Four of five anti-CCP positive patients in our study were more than 10 years old at onset; the fifth was one year old and had systemic JIA.…”

Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus

“…RF-positive arthritis was considered the pediatric counterpart of adult RF-positive RA. Several aspects support this assumption: (1) the clinical phenotype is the same and is characterized by female predominance, late onset, and a symmetric arthritis affecting principally wrists and the small joints of the hands and feet; (2) it usually has a progressive course and indeed, among the various JIA categories, it is the one with the worst prognosis 33 ; (3) it is the only JIA category in which positive antibodies to CCP have been found 34,35 ; and (4) it shares with adult RF-positive RA the same HLA associations 7 . At variance with adults, it represents just a small proportion (around 5%) of childhood chronic arthritis.…”

Age-related diagnostic utility of rheumatoid factor, anticyclic citrullinated peptide and antikeratin antibodies in Chinese patients with rheumatoid arthritis

“…Studies have suggested an association between JIA and interleukin (IL) 6 polymorphism, 23 as well as the presence of anticitrullinated type II collagen and anticitrullinated fibrinogen antibodies. 24 It is likely that a combination of IL-6 genotyping and the detection of anticitrullinated type II collagen and anticitrullinated fibrinogen antibodies may be a useful diagnostic approach for JIA.…”