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Background: Antibodies to histone have been associated in the adult literature with systemic lupus erythematosus(SLE) and drug induced lupus(DILE). Little data is available regarding the spectrum of pathology that antibodies to histone encompass in the pediatric population. Prior studies suggest an association with SLE, juvenile idiopathic arthritis(JIA), uveitis and linear scleroderma. Methods: Patient charts were reviewed that contained positive anti-histone antibody testing during a consecutive three year period. Patient diagnosis along with the presence of: anti-histone antibody titer, ANA, and the presence of other autoantibodies to SSA, SSB, Sm, RNP, dsDNA and chromatin were obtained. The frequency of SLE, JIA and DILE was further investigated in specific subsets. Results: 139 individual charts were reviewed containing 41 different diagnoses. The most common diagnosis was hypermobility arthralgia with 22 patients. The most frequent rheumatologic diagnosis was JIA(nonsystemic) with 19. 13 patients in this study were diagnosed with SLE and 2 with DILE. 18 patients had other autoantibody production, of these, 11 had SLE or DILE. Only one of 62 patients with a weak antihistone antibody titer(1.0-1.5) was diagnosed with SLE. When strong titers are present(> 2.5), the antihistone antibody test was associated with a greater than 50% incidence of an underlying rheumatologic disease and ten times higher incidence of SLE than a weak titer. In regards to the frequency of SLE, there was a statistically significant difference between weak and moderate titers and between weak and strong titers. Conclusion: The presence of anti-histone antibody was observed in a variety of diagnoses in the pediatric population. Overall, the presence of anti-histone antibodies appears to have poor diagnostic utility for any specific condition. However, diagnostic utility for SLE does appear to improve with higher titers, when combined with other autoantibody positivity. Strength of titer did not appear to be a factor for JIA, but was the most frequently observed rheumatologic disease in this study. [ABSTRACT FROM AUTHOR]

Background: To 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). Methods: Sera 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 a-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. Results: Twenty-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 anticitrullinated 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%. Conclusion: This 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. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis (JIA) reflects a group of clinically heterogeneous, autoimmune disorders in children characterized by chronic arthritis and hallmarked by elevated levels of circulating immune complexes (CICs) and associated complement activation by-products in their sera. Immune complexes (ICs) have been detected in patients' sera with JIA utilizing a variety of methods, including the anti-human IgM affinity column, C1q solid-phase assay, polyethylene glycol precipitation, Staphylococcal Protein A separation method, anti-C1q/C3 affinity columns, and FcγRIII affinity method. As many as 75% of JIA patients have had IC detected in their sera. The CIC proteome in JIA patients has been examined to elucidate disease-associated proteins that are expressed in active disease. Evaluation of these ICs has shown the presence of multiple peptide fragments by SDS-PAGE and 2-DE. Subsequently, all isotypes of rheumatoid factor (RF), isotypes of anti-cyclic citrullinated peptide (CCP) antibodies, IgG, C1q, C4, C3, and the membrane attack complex (MAC) were detected in these IC. Complement activation and levels of IC correlate with disease activity in JIA, indicating their role in the pathophysiology of the disease. This review will summarize the existing literature and discuss the role of possible protein modification that participates in the generation of the immune response. We will address the possible role of these events in the development of ectopic germinal centers that become the secondary site of plasma cell development in JIA. We will further address possible therapeutic modalities that could be instituted as a result of the information gathered by the presence of ICs in JIA. [ABSTRACT FROM AUTHOR]

Background/Purpose: IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified in the sera of juvenile idiopathic arthritis (JIA) patients and have been associated with more destructive disease. The identity of the target proteins of the citrullinated modification has remained elusive. We attempted to determine the prevalence and significance of different citrullinated epitopes. Methods: We evaluated serum from 96 patients with various subtypes of JIA for the presence of antideiminated (citrullinated) fibrinogen, anti-citrullinated α-enolase, anti-citrullinated and native type II collagen, and anti-vimentin (vim1-16 and vim 59-74) antibodies by enzyme-linked immunosorbent assays. We correlated the presence of the antibodies with anti-CCP and rheumatoid factor (RF) isotypes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. Results: 31 JIA patients (32%) demonstrated reactivity to anti-citrullinated fibrinogen, 23 (24%) to anti-citrullinated type II collagen, 10 (10.5%) to anticitrullinated vimentin I-16, 9 (9%) to anti-citrullinated α-enolase, and 7 (7.4%) to anti-citrullinated vimentin 59-74 antibodies. One IgM RF positive JIA patient was positive for all 6 of the citrullinated autobodies assayed. The reactivity was higher in those JIA patients positive for IgM RF and IgG/IgM anti-CCP antibodies. Conclusion: The study demonstrates that antibodies to multiple citrullinated epitopes are present in the sera of patients with JIA. A higher percentage of antibodies reacted with citrullinated fibrinogen and citrullinated type II collagen. The more widespread the positivity correlates with more severe disease. [ABSTRACT FROM AUTHOR]

Abstract: Introduction.: Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic autoimmune diseases with variable clinical outcomes. We investigated whether the synovial fluid (SF) proteome could distinguish a subset of patients in whom disease extends to affect a large number of joints. Methods.: SF samples from 57 patients were obtained around time of initial diagnosis of JIA, labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with expression verified by immunochemical methods. Protein glycosylation status was confirmed by hydrophilic interaction liquid chromatography. Results.: A truncated isoform of vitamin D binding protein (VDBP) is present at significantly reduced levels in the SF of oligoarticular patients at risk of disease extension, relative to other subgroups (p <0.05). Furthermore, sialylated forms of immunopurified synovial VDBP were significantly reduced in extended oligoarticular patients (p <0.005). Conclusion.: Reduced conversion of VDBP to a macrophage activation factor may be used to stratify patients to determine risk of disease extension in JIA patients. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]