Mapping of B-Cell Epitopes Recognized by Antibodies to Histones in Subsets of Juvenile Chronic Arthritis
ABSTRACT 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.
- SourceAvailable from: Henner Morbach
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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  . Anti-CCP antibodies seemed to be associated with a more severe disease progress in RA patients . "
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.12/2010; 2010:759868. DOI:10.1155/2010/759868
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ABSTRACT: We have recently found that antibodies to total histones are common in a group of American patients with type 1 autoimmune hepatitis (AIH). In an attempt to determine the profile and clinical association of anti-histone antibody (AHA), 45 Japanese AIH patients were studied for serum isotypic reactivity with individual histones (H1, H2A, H2B, H3, H4) by enzyme-linked immunosorbent assay and western blotting. The results revealed that 40% of sera had reactivities with at least one of individual histones and that the antibodies were detected in all three classes of immunoglobulins (IgG, IgM, IgA). Immunoglobulin G type anti-H3 showed the dominant reactivity and it characterized 72% of sera with AHA. The titre of anti-H3 decreased significantly (P < 0.0075) after steroid therapy and the index of decrease for anti-H3 was correlated in individuals with that for serum aminotransferase. In general, patients with AHA showed higher serum level of alanine aminotransferase (P < 0.05), immunoglobulin G (P < 0.025), and higher frequency of A2-DR4 haplotype (53 vs 17%) than their seronegative counterparts. However, the titre of AHA was low in this disease condition and histone class-specific antibodies did not distinguish patients with distinctive clinical features, although patients with anti-H3 tended to be younger than those without AHA.Journal of Gastroenterology and Hepatology 06/1998; 13(5):483-9. DOI:10.1111/j.1440-1746.1998.tb00673.x
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ABSTRACT: Up to one-half of patients with anterior uveitis suffer from related systemic diseases. The common associations are the seronegative arthropathies and, in children, juvenile chronic arthritis. Anterior uveitis may also occur in the context of sarcoidosis or Behçet's disease. Syphilis and tuberculosis remain a significant problem for specific populations and may be the cause of anterior uveitis in these groups. By thorough clinical history and the correct selection and interpretation of simple investigations, it is generally possible for the ophthalmologist to make or exclude a systemic diagnosis, predict the ocular prognosis and direct selected patients to the appropriate physician. Diseases that threaten the patient's wellbeing must certainly be recognized. In the present review we present a method for identifying the systemic associations of anterior uveitis.Australian and New Zealand Journal of Ophthalmology 10/1998; 26(4):319 - 326. DOI:10.1111/j.1442-9071.1998.tb01336.x