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风湿热和风湿性心脏病的免疫学与免疫遗传学研究。

Immunologic and immunogenetic studies in rheumatic fever and rheumatic heart disease.

作者信息

Reddy K S, Narula J, Bhatia R, Shailendri K, Koicha M, Taneja V, Jhingan B, Pothineni R B, Malaviya A N, Mehra N K

机构信息

Department of Cardiology, Medicine and Anatomy, All India Institute of Medical Sciences, New Delhi.

出版信息

Indian J Pediatr. 1990 Sep-Oct;57(5):693-700. doi: 10.1007/BF02728716.

DOI:10.1007/BF02728716
PMID:2094670
Abstract

In order to evaluate all the important limbs of the immune system in the same patient population with rheumatic fever (RF) and rheumatic heart disease (RHD) cellular and humoral immune parameters as well as the immunogenetic profile in 265 North Indian patients with RHD were evaluated. They were studied for class in HLA antigens and 165 of them were also evaluated for the class II (DR locus) antigen profile. Data obtained was compared with 400 and 134 healthy controls respectively of the same ethnicity. Humoral immune parameters (Serum immunoglobulins IgG, IgA; Serum complement fractions C3, C4, C3d; circulating immune complexes and B lymphocyte numbers) and cellular immune parameters (total leucocyte and lymphocyte counts; T lymphocyte sub-populations--CD4, CD8 counts; lymphocyte migration inhibition to an extracellular streptococcal antigen, streptolysin 'O') were studied in 23 patients with RF, 21 patients with "inactive" RHD and 20 normal controls. Patients of RHD were noted to have an increased frequency of DR3 (P less than 0.001; Relative risk = 2.3) and a decreased frequency of DR2 (P less than 0.001; Relative risk = 0.3) as compared to the controls. Patients of RF had evidence of an altered regulatory T cell function (increased CD4/CD8 ratio) and decreased cell mediated immunity to streptolysin 'O'. An increased humoral immune response (increased B cell counts, elevated serum IgG, circulating immune complexes and C3d) was noted in patients of RF as well as "inactive" RHD. An integrated pathogenetic model with immune response associated antigens of the DR locus influencing selection of cardiac cross-reactive antigens by the antigen processing macrophages, an altered regulatory T cell function with decreased suppressor T cell activity leading to an abnormal immune response is proposed to explain the pathogenesis of RF.

摘要

为了在同一风湿热(RF)和风湿性心脏病(RHD)患者群体中评估免疫系统的所有重要分支,对265名北印度RHD患者的细胞和体液免疫参数以及免疫遗传学特征进行了评估。对他们进行了HLA抗原分型研究,其中165人还评估了II类(DR位点)抗原谱。分别将获得的数据与400名和134名相同种族的健康对照进行比较。在23名RF患者、21名“非活动期”RHD患者和20名正常对照中研究了体液免疫参数(血清免疫球蛋白IgG、IgA;血清补体成分C3、C4、C3d;循环免疫复合物和B淋巴细胞数量)和细胞免疫参数(白细胞和淋巴细胞总数;T淋巴细胞亚群——CD4、CD8计数;淋巴细胞对细胞外链球菌抗原链球菌溶血素“O”的迁移抑制)。与对照组相比,RHD患者的DR3频率增加(P<0.001;相对风险=2.3),DR2频率降低(P<0.001;相对风险=0.3)。RF患者有调节性T细胞功能改变(CD4/CD8比值增加)和对链球菌溶血素“O”的细胞介导免疫降低的证据。在RF患者以及“非活动期”RHD患者中发现体液免疫反应增强(B细胞计数增加、血清IgG升高、循环免疫复合物和C3d升高)。提出了一个综合发病机制模型,即DR位点的免疫反应相关抗原影响抗原加工巨噬细胞对心脏交叉反应抗原的选择,调节性T细胞功能改变,抑制性T细胞活性降低导致异常免疫反应,以解释RF的发病机制。

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