Association of HLA-DR, DQ Genotype With Different β-Cell Functions at IDDM Diagnosis in Japanese Children
Association of HLA-DR, DQ Genotype With Different β-Cell Functions at IDDM Diagnosis in Japanese Children
复制标题
日本儿童 IDDM 诊断中 HLA-DR、DQ 基因型与不同 β 细胞功能的关联
作者：
S. Sugihara;T. Sakamaki;S. Konda;A. Murata;K. Wataki;Y. Kobayashi;K. Minamitani;S. Miyamoto;N. Sasaki;Hiroo Niimi
日本IDDM患者已被证明具有独特的和不同的HLA协会从白色患者。为了阐明日本人胰岛素依赖型糖尿病临床异质性的HLA相关遗传因素的影响，采用聚合酶链反应-序列特异性寡核苷酸（PCR-SSO）或序列特异性引物（SSP）检测了88例日本儿童期胰岛素依赖型糖尿病患者的HLA-DRB 1、DQA 1和DQB 1基因型。在88例IDDM患者中，26例（29.5%）为DRB 1 *0405-DQA 1 *0302-DQB 1 *0401/X（DR 4-DQ 4/X），38例（43.2%）为DRB 1 *0901-DQA 1 * 0302-DQB 1 *0303/X（DR 9-DQ 9/X），9例（10.2%）为DR 4/9-DQ 4/9杂合子（X不含保护性等位基因）。比较HLA-DR 4-DQ 4和DR 9-DQ 9患者的临床异质性，如发病时的年龄分布、患病率和血清抗GAD抗体（GADAb）水平，以及诊断后残留的胰腺β细胞功能。发病年龄较低（0-10岁）组DR 9-DQ 9基因型频率明显高于发病年龄较大（11-16岁）组，而发病年龄较大（11 -16岁）组DR 4-DQ 4基因型频率明显高于发病年龄较大（11-16岁）组。虽然在新诊断的患者中未发现DR-DQ基因型与GADAb的患病率和血清水平相关，但长期DR 9-DQ 9患者的GADAb水平显著高于DR 4-DQ 4患者。虽然在GADAb+和GADAb−患者之间没有检测到血清C肽（CPR）水平的时间过程差异，但在DR 9-DQ 9和DR 4-DQ 4患者之间证明了显著差异。在诊断时至诊断后12-18个月，DR 4-DQ 4患者的残余胰腺β细胞功能比DR 9-DQ 9患者保留更多。这些结果表明，DR 9-DQ 9基因型可能比DR 4-DQ 4基因型诱导更强的针对靶β细胞的自身免疫破坏性反应（T-helper 1功能）。我们的研究结果可能需要进一步研究糖尿病自身免疫反应与HLA II类分子的关联，并有助于澄清HLA编码的IDDM易感性的种族间差异。
Japanese IDDM patients have been demonstrated to have unique and different HLA associations from white patients. To elucidate the effect of HLA-associated genetic factors on the clinical heterogeneity of IDDM in Japanese people, HLA-DRB1, DQA1, and DQB1 genotypes in 88 childhood-onset Japanese IDDM patients were examined by polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) or sequence-specific primers (SSP). Of the 88 IDDM patients, 26 (29.5%) had DRB1*0405-DQA1*0302-DQB1*0401/X (DR4-DQ4/X), 38 (43.2%) had DRB1*0901-DQA1*0302-DQB1*0303/X (DR9-DQ9/X), and 9 (10.2%) were DR4/9-DQ4/9 heterozygous in the present study (X does not contain protective alleles). Clinical heterogeneity such as age distribution at onset, prevalence and serum level of anti-GAD antibodies (GADAb), and residual pancreatic β-cell function after diagnosis were compared between patients with HLA-DR4-DQ4 and DR9-DQ9. The frequency of DR9-DQ9 genotype was significantly higher in the younger (0–10 years) than in the older (11–16 years) age-group of onset, but the frequency of DR4-DQ4 was higher in the older (11–16 years) age-group. Although no association of DR-DQ genotypes with the prevalence and serum level of GADAb was found among newly diagnosed patients, long-standing DR9-DQ9 patients had significantly higher levels of GADAb than those with DR4-DQ4. While no difference in time course of serum C-peptide (CPR) levels was detected between GADAb+ and GADAb− patients, a remarkable difference was demonstrated between DR9-DQ9 and DR4-DQ4 patients. The residual pancreatic β-cell function was retained more in patients with DR4-DQ4 than in those with DR9-DQ9 at diagnosis through 12–18 months after diagnosis. These results suggest that the DR9-DQ9 genotype may induce stronger autoimmune destructive response (T-helper 1 function) against target β-cells than the DR4-DQ4 genotype does. Our findings may warrant further studies on the association of diabetogenic autoimmune response with HLA class II molecules and contribute to a clarification of interracial differences in HLA-encoded susceptibility to IDDM.
功能性 CD4 T 细胞亚群在完整的免疫系统中相互作用。
DOI：
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发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Murray,JS;Madri,J;Pasqualini,T;Bottomly,K
通讯作者：
Bottomly,K