BackgroundSeveral studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP) antibodies in juvenile idiopathic arthritis (JIA) as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated) fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes.MethodsSera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA). In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF) isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA.ResultsThirty-one JIA patients (32%) demonstrated reactivity to citrullinated fibrinogen and 9 (9%) to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and IgM RF. The presence of anti-citrullinated α-enolase antibodies correlated with IgA anti-CCP antibodies. IgG anti-CCP antibodies were significantly associated with joint damage and anti-citrullinated fibrinogen antibodies were strongly associated with JIA when compared to control groups. Anti-citrullinated fibrinogen antibodies demonstrated high sensitivity (81%) for IgM RF-positive polyarticular JIA. IgG anti-CCP antibodies had the highest specificity (95%) for JIA, with anti-citrullinated fibrinogen antibodies, IgA anti-CCP antibodies and IgA RF all following at 84%.ConclusionsJIA patient sera exhibited strong reactivity to anti-citrullinated fibrinogen antibodies and demonstrated high sensitivity and specificity for JIA, primarily in IgM RF-positive polyarthritis patients. Fibrinogen is one of several protein targets for citrullination in JIA.

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Circulating immune complexes (CICs) from juvenile idiopathic arthritis (JIA) sera have been shown to contain bound complement components; however, whether the classical or alternative pathway is the main pathway involved remains undetermined. To delineate the role of these pathways in the disease process, we measured activated complement products bound to CICs in sera from 100 JIA patients.

It is well known that parvovirus B19 causes erythema infectiosum, a common febrile exanthema of childhood. Studies have also shown that parvovirus B19 can cause chronic arthropathy in children, and some children may meet classification criteria for juvenile idiopathic arthritis. A child's anti-B19 antibodies may cross-react with other antigens leading to autoantibody formation and immune complex deposition. This process can cause a similar clinical picture to systemic lupus erythematosus, and in some cases has been implicated in initiation of disease. Parvovirus B19 has also been linked to the presence of antiphospholipid antibodies, juvenile dermatomyositis, vasculitides, immune thrombocytopenic purpura, and hemophagocytic lymphohistiocytosis. This review provides an extensive evaluation of the literature on parvovirus B19 and its role in rheumatic diseases in children.

Epstein-Barr virus (EBV) is known to cause infectious mononucleosis; in addition, it is strongly associated with malignancies. Studies have also demonstrated that EBV infection may trigger the development of systemic lupus erythematosus. EBV infection has been implicated in complicating treatment of juvenile idiopathic arthritis, in addition to triggering cytokine production. Awareness of a past or present EBV infection has been highlighted as an important factor in determining treatment options in several diseases. Repeated associations have been described between EBV infection and various rheumatic diseases and complications of rheumatic disease, including Kawasaki disease, immune thrombocytopenic purpura, and hemophagocytic lymphohistiocytosis. We present a review of recent literature demonstrating the significance of EBV infection in rheumatic diseases, and complications of rheumatic disease, in children.