Handa Tomohiro, Nagai Sonoko, Ito Isao, Shigematsu Michio, Hamada Kunio, Kitaichi Masanori, Izumi Takateru, Mishima Michiaki
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Sarcoidosis Vasc Diffuse Lung Dis. 2003 Oct;20(3):190-6.
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.
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.
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).
CTLA-4 exonl polymorphism might affect BAL fluid lymphocyte profiles in Japanese sarcoidosis patients.
结节病是一种全身性疾病，其特征为T细胞活化以及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中的一个关键因素，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）是活化T细胞上表达的T细胞活化负调节因子。先前已描述CTLA-4外显子1多态性的G等位基因与几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中CTLA-4与疾病易感性及支气管肺泡灌洗（BAL）中细胞谱的关系。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对135例日本结节病患者和97例对照进行CTLA-4外显子1 A/G双等位基因多态性分型，并比较两组基因型的分布。67例患者接受了BAL检查，比较了G/G基因型患者和A/A基因型患者BAL液中的细胞谱。
结节病患者（GG：46%，AG：39%，AA：15%）与对照（GG：42%，AG：49%，AA：8%）之间基因型和等位基因频率分布无显著差异。与A/A基因型患者相比，G/G基因型患者BAL液中的淋巴细胞比例、淋巴细胞计数和CD4(+)细胞计数显著增加（p < 0.05）。
CTLA-4外显子1多态性可能影响日本结节病患者BAL液中的淋巴细胞谱。
