Cytotoxic T-lymphocyte antigen-4 (CTLA-4) exon 1 polymorphism affects lymphocyte profiles in bronchoalveolar lavage of patients with sarcoidosis.
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) exon 1 polymorphism affects lymphocyte profiles in bronchoalveolar lavage of patients with sarcoidosis.
复制标题
细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 外显子 1 多态性影响结节病患者支气管肺泡灌洗液中的淋巴细胞谱。
DOI：
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
M. Mishima
中科院分区：
文献类型：
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作者：
T. Handa;S. Nagai;I. Ito;M. Shigematsu;K. Hamada;M. Kitaichi;T. Izumi;M. Mishima
背景
结节病是一种全身性疾病，其特征是 T 细胞激活并随后在受累部位形成肉芽肿。遗传易感性是该疾病发病机制的关键因素，参与 T 细胞调节的基因是潜在的候选基因。细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 是表达在活化 T 细胞上的 T 细胞活化负调节因子。 CTLA-4 外显子 1 多态性的 G 等位基因先前已被描述与多种自身免疫性疾病的疾病易感性相关。我们研究了日本结节病患者的 CTLA-4 与疾病易感性和支气管肺泡灌洗 (BAL) 细胞谱的关系。
方法
使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对日本结节病患者（n = 135）和对照（n = 97）进行CTLA-4外显子1中的A/G双等位基因多态性分型，并比较两组之间的基因型分布。 67 名患者接受了 BAL，并对 G/G 基因型和 A/A 基因型患者的 BAL 液中的细胞谱进行了比较。
结果
结节病（GG：46％，AG：39％，AA：15％）和对照（GG：42％，AG：49％，AA：8％）之间基因型和等位基因频率的分布没有显着差异。与A/A基因型患者相比，G/G基因型患者的BAL液中淋巴细胞比率、淋巴细胞计数和CD4(+)细胞计数显着增加(p < 0.05)。
结论
CTLA-4 外显子多态性可能影响日本结节病患者的 BAL 液淋巴细胞谱。
BACKGROUND
Sarcoidosis is a systemic disease characterized by T-cell activation and subsequent granuloma formation at the site of involvement. Genetic susceptibility is a key factor in the pathogenesis of this disease, and genes involved in T-cell regulation are potential candidates. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation expressed on activated T-cells. The G allele of the CTLA-4 exon 1 polymorphism has previously been described to be associated with disease susceptibility in several autoimmune diseases. We investigated the relationship of CTLA-4 to disease susceptibility and cell profiles in bronchoalveolar lavage (BAL) in Japanese sarcoidosis patients.
METHODS
Japanese sarcoidosis patients (n = 135) and controls (n = 97) were typed for an A/G bi-allelic polymorphism in exon 1 of CTLA-4 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the distribution of genotypes was compared between both groups. Sixty-seven patients underwent BAL, and cell profiles in BAL fluid were compared between patients with G/G genotype and those with A/A genotype.
RESULTS
No significant differences in the distribution of genotype and allele frequencies were found between sarcoidosis (GG: 46%, AG: 39%, AA: 15%) and controls (GG: 42%, AG: 49%, AA: 8%). Patients with G/G genotype had significantly increased lymphocyte ratios, lymphocyte counts, and CD4(+) cell counts in BAL fluid compared with patients with A/A genotype (p < 0.05).
CONCLUSIONS
CTLA-4 exonl polymorphism might affect BAL fluid lymphocyte profiles in Japanese sarcoidosis patients.