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青少年慢性关节炎亚组中抗组蛋白抗体识别的B细胞表位图谱

Mapping of B-cell epitopes recognized by antibodies to histones in subsets of juvenile chronic arthritis.

作者信息

Stemmer C, Tuaillon N, Prieur A M, Muller S

机构信息

Institut de Biologie Moléculaire et Cellulaire, UPR 9021, CNRS, Strasbourg, France.

出版信息

Clin Immunol Immunopathol. 1995 Jul;76(1 Pt 1):82-9. doi: 10.1006/clin.1995.1091.

DOI:10.1006/clin.1995.1091
PMID:7541736
Abstract

The sera of 138 patients with juvenile chronic arthritis (JCA) were tested in ELISA with the five individual histones, 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.

摘要

采用酶联免疫吸附测定法(ELISA),使用5种单个组蛋白、覆盖4种核心组蛋白全长的34种组蛋白肽段以及对应于H1 N端和C端结构域的2种肽段,对138例青少年慢性关节炎(JCA)患者的血清进行检测。针对JCA的不同亚组(少关节型、多关节型和全身型起病)、临床特征(慢性前葡萄膜炎,CAU)以及其他血清学特征(抗核抗体,ANA),检测IgG抗体的出现情况。138份血清中,72%与至少1种组蛋白肽段发生反应。H1的204 - 218肽段、H2B的1 - 25肽段以及H3的111 - 130肽段被22% - 28%的JCA血清识别,42%的JCA血清与H2B的1 - 25肽段和H3的111 - 130肽段中的一种或两种发生反应。在JCA的三个亚组中,抗组蛋白抗体(AHA)针对组蛋白组分类型(H1、H2A、H2B、H3和H4)或组蛋白区域的出现频率无显著差异。未发现针对组蛋白肽段的IgG抗体与葡萄膜炎之间存在明显关联。在少关节型JCA亚组中,13/31例(41.9%)患有CAU的患者与14/41例(34.1%)未患CAU的患者相比,拥有与H3 C端结构域83 - 135肽段发生反应的IgG抗体。这种差异无统计学意义。最后,针对组蛋白和组蛋白肽段的抗体不能完全解释患者血清中发现的ANA反应性。尽管针对组蛋白肽段的抗体在JCA患儿血清中频繁出现,但抗体谱似乎具有高度个体性,且与疾病亚型或活动度无关。识别不仅存在于循环中而且存在于组织沉积物中的AHA可能有助于更好地识别致病性抗体。

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