Mapping of B-Cell Epitopes Recognized by Antibodies to Histones in Subsets of Juvenile Chronic Arthritis

Institut de Biologie Moléculaire et Cellulaire, UPR 9021, CNRS, Strasbourg, France
Clinical Immunology and Immunopathology 08/1995; 76(1):82-89. DOI: 10.1006/clin.1995.1091


The sera of 138 patients with juvenile chronic arthritis (JCA) were tested in ELISA with the five individual histories, 34 histone peptides covering the full length of the four core histones, and two peptides corresponding to the N- and C-terminal domains of H1. The occurrence of IgG antibodies was examined regarding the different subsets of JCA (pauciarticular, polyarticular, and systemic onset) and regarding clinical features (chronic anterior uveitis, CAU) and other serological features (antinuclear antibodies, ANA). Seventy-two percent of the 138 sera reacted with at least 1 histone peptide. The peptides 204-218 of H1, 1-25 of H2B, and 111-130 of H3 were recognized by 22-28% of JCA sera, and 42% of JCA sera reacted with one or both peptides 1-25 of H2B and 111-130 of H3. The frequency of occurrence of anti-histone antibodies (AHA) regarding the type of histone fraction (H1, H2A, H2B, H3 and H4) or the regions of histones was not significantly different in the three subsets of JCA. No obvious association was found between IgG antibodies to histone peptides and uveitis. In the subset of pauciarticular JCA, 13/31 patients (41.9%) with CAU against 14/41 patients (34.1%) without CAU possessed IgG antibodies reacting with peptides of the C-terminal domain 83-135 of H3. This difference is not statistically significant. Finally, the presence of antibodies to histones and histone peptides cannot completely explain ANA reactivity found in patients' sera. Although antibodies to histone peptides occur frequently in the serum of children with JCA, the antibody profiles seem to be highly individual and do not correlate with disease subtype or activity. Identification of AHA present not only in the circulation but also in tissue deposits may provide better insight into the identification of pathogenic antibodies.

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    • "In particular, antibodies against cyclic citrullinated peptide (anti-CCP) as well as against mutated citrullinated vimentin (anti-MCV) have been documented in the RF positive polyarticular subgroups of JIA patients, but not in other subgroups [10–12, 14, 18, 27, 28, 32, 35, 37]. These autoantibodies yielded higher specificity in diagnosing RA and might distinguish a characteristic group of polyarticular JIA patients as well [26] [28]. Anti-CCP antibodies seemed to be associated with a more severe disease progress in RA patients [38]. "
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    ABSTRACT: Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic arthritis in childhood and adolescents and encompasses a heterogeneous group of different diseases. Due to the promising results of B-cell depleting therapies in rheumatoid arthritis the role of B-cells in autoimmune diseases has to be discussed in a new context. Additionally, experiments in mouse models have shed new light on the antibody-independent role of B-cells in the development of autoimmune diseases. In this review we will discuss the importance of B-cells in the pathogenesis of JIA appraising the question for an immunological basis of B-cell targeted therapy in JIA.
    Full-text · Article · Dec 2010
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    ABSTRACT: We have shown previously that four IgG monoclonal autoantibodies (mAbs) reacted in ELISA with both double-stranded (ds) DNA and peptide 83-100 of histone H3. The peptide 83-100 contains a cysteine residue at position 96 and readily dimerizes at pH 7-8. We describe here that only the 83-100 dimers, and not the 83-100 monomers, are recognized by the four antibodies and inhibit in ELISA the binding of mAbs to dsDNA. The equilibrium affinity constants (Ka) and kinetic rate constants of two of these mAbs were measured in a biosensor system. Ka values were significantly higher when these mAbs were tested with dsDNA as compared with the 83-100 dimer. Further higher Ka values were measured with mononucleosomes containing DNA and histones. It is proposed that these four mAbs are directed against a topographic determinant formed by DNA and the region 83-100 of H3 present as a dimer at the surface of nucleosome, and that they react, although significantly less well, with DNA and peptide dimer tested separately. This study provides a quantitative and kinetic basis to interaction between several antibodies and distinct antigenic structures and allows us to better understand the structural basis of apparent autoantibody cross-reactivity.
    Full-text · Article · Sep 1996 · Journal of Biological Chemistry
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    ABSTRACT: This chapter focuses on anti-histone antibodies (AHA) excluding (H2A-H2B)-DNA autoantibodies. AHA are found in a number of systemic diseases such as systemic lupus erythematosus (SLE), drug-induced lupus, rheumatoid arthritis (RA), juvenile chronic arthritis, Feltys syndrome, localized scleroderma, and systemic sclerosis. Lupus mice of different genetic backgrounds are used to study the production and specificity of AHA during the course of the disease and for analyzing their possible role in pathogenesis. AHAs are found in a number of systemic and organ-specific autoimmune diseases as well as in neurological diseases and certain infections including infectious mononucleosis. Experiments suggest that DNA and histones circulate in some SLE patients as oligonucleosome-like complexes that are potentially available for forming complexes with anti-DNA antibodies.
    No preview · Chapter · Dec 1996
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