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韩国胰岛素依赖型糖尿病患者中64k自身抗体、胰岛β细胞功能、HLA - DR抗原与HLA - DQ基因之间的关系。

Relationships among 64k autoantibodies, pancreatic beta-cell function, HLA-DR antigens and HLA-DQ genes in patients with insulin-dependent diabetes mellitus in Korea.

作者信息

Lee H C, Cha B S, Nam M S, Song Y D, Lim S K, Kim D H, Huh K B, Koh Y

机构信息

Department of Internal Medicine, Pediatrics, Yonsei University, College of Medicine, Seoul, Korea.

出版信息

Korean J Intern Med. 1995 Jan;10(1):1-9. doi: 10.3904/kjim.1995.10.1.1.

DOI:10.3904/kjim.1995.10.1.1
PMID:7626550
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4532034/
Abstract

OBJECTIVES

Among autoantibodies detected in patients with insulin-dependent diabetes mellitus (IDDM), antibodies to 64,000(Mr) islet protein(64k), now recognized as glutamic acid decarboxylase(GAD), appear to be an even more predictive marker of IDDM than islet cytoplasmic antibody (ICA) or insulin autoantibody (IAA). We examined the relationships among 64k autoantibodies, pancreatic beta-cell function, HLA-DR antigens and HLA-DQ genes in patients with IDDM in Korea.

METHODS

To identify the 64k autoantibody, the immunoprecipitation method was performed for 35 patients with IDDM and 10 normal controls. In patients with IDDM, serum C-peptide levels were measured and HLA-DR typings and HLA-DQA1 and DQB1 gene typings were performed.

RESULTS

12 of 35 (34%) patients with IDDM were positive for 64k autoantibody in contrast to none of 10(0%) normal controls. There were no differences in residual pancreatic beta-cell function between 64k autoantibody positive and negative groups. 64k autoantibody was detected more frequently in patients with recent (duration < 6 months, 10/25[40%]) and young -aged(aged < 15 years, 7/18[39%]) onset of IDDM. All of 3(100%) patients with HLA-DR3/DR4 heterotypes were positive in 64k autoantibody, in contrast to 1 of 7(14%) patients without HLA-DR3 nor DR4. The frequencies of HLA-DQA10301, HLA-DQB10201, DQB1* 0302 and DQB1*0303 gene types were higher in patients with 64k autoantibody (12/12 [100%]) vs. without 64k autoantibody 18/22[81%], 5/11[45%] vs. without 64k autoantibody 5/22[23%], 5/11[45%] vs. without 64k autoantibody 8/22[36%] and 6/11 [55%] vs. without 64k autoantibody 9/22[41%].

CONCLUSIONS

There results suggest that 64k autoantibodies have some relationship with HLA-DR, DQA1 and DQB1 genes, but not with residual pancreatic beta-cell function in Korean patients with IDDM.

摘要

目的

在胰岛素依赖型糖尿病(IDDM)患者检测出的自身抗体中,针对64,000(Mr)胰岛蛋白(64k)的抗体,现被认为是谷氨酸脱羧酶(GAD),与胰岛细胞浆抗体(ICA)或胰岛素自身抗体(IAA)相比,似乎是IDDM更具预测性的标志物。我们研究了韩国IDDM患者中64k自身抗体、胰岛β细胞功能、HLA - DR抗原和HLA - DQ基因之间的关系。

方法

为鉴定64k自身抗体,对35例IDDM患者和10例正常对照进行了免疫沉淀法检测。对IDDM患者测定血清C肽水平,并进行HLA - DR分型以及HLA - DQA1和DQB1基因分型。

结果

35例IDDM患者中有12例(34%)64k自身抗体呈阳性,而10例正常对照均为阴性(0%)。64k自身抗体阳性和阴性组之间残留的胰岛β细胞功能无差异。64k自身抗体在近期发病(病程<6个月,10/25[40%])和年轻(年龄<15岁,7/18[39%])的IDDM患者中检出频率更高。3例(100%)HLA - DR3/DR4异型患者64k自身抗体均呈阳性,而7例无HLA - DR3和DR4的患者中有1例(14%)呈阳性。64k自身抗体阳性患者中HLA - DQA10301、HLA - DQB10201、DQB10302和DQB10303基因类型的频率高于无64k自身抗体的患者(分别为12/12[100%]对18/22[81%]、5/11[45%]对5/22[23%]、5/11[45%]对8/22[36%]、6/11[55%]对9/22[41%])。

结论

这些结果表明,在韩国IDDM患者中,64k自身抗体与HLA - DR、DQA1和DQB1基因存在一定关系,但与残留的胰岛β细胞功能无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8112/4532034/a4d8addc3feb/kjim-10-1-1-1f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8112/4532034/a4d8addc3feb/kjim-10-1-1-1f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8112/4532034/a4d8addc3feb/kjim-10-1-1-1f1.jpg

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本文引用的文献

1
Autoantibodies in IDDM primarily recognize the 65,000-M(r) rather than the 67,000-M(r) isoform of glutamic acid decarboxylase.胰岛素依赖型糖尿病中的自身抗体主要识别的是分子量为65,000的谷氨酸脱羧酶异构体,而非分子量为67,000的异构体。
Diabetes. 1993 Apr;42(4):631-6. doi: 10.2337/diab.42.4.631.
2
Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease.谷氨酸脱羧酶抗体可揭示非胰岛素依赖型起病的成人隐匿性自身免疫性糖尿病。
Diabetes. 1993 Feb;42(2):359-62. doi: 10.2337/diab.42.2.359.
3
Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.
使用重组人胰岛谷氨酸脱羧酶(GAD65)进行的定量测定表明,发病时64K自身抗体阳性可预测糖尿病类型。
J Clin Invest. 1993 Jan;91(1):368-74. doi: 10.1172/JCI116195.
4
Detection of GAD65 antibodies in diabetes and other autoimmune diseases using a simple radioligand assay.使用简单放射性配体分析法检测糖尿病及其他自身免疫性疾病中的GAD65抗体。
Diabetes. 1994 Mar;43(3):459-67. doi: 10.2337/diab.43.3.459.
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Diabetes. 1994 Mar;43(3):418-25. doi: 10.2337/diab.43.3.418.
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Diabetologia. 1993 Nov;36(11):1210-1. doi: 10.1007/BF00401069.
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Insulin autoantibodies and high titre islet cell antibodies are preferentially associated with the HLA DQA1*0301-DQB1*0302 haplotype at clinical type 1 (insulin-dependent) diabetes mellitus before age 10 years, but not at onset between age 10 and 40 years. The Belgian Diabetes Registry.胰岛素自身抗体和高滴度胰岛细胞抗体在10岁前的临床1型(胰岛素依赖型)糖尿病中优先与HLA DQA1*0301-DQB1*0302单倍型相关,但在10至40岁发病时则不然。比利时糖尿病登记处。
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