EVIDENCE OF AN ACCELERATED B-CELL DESTRUCTION IN HLA-DW3/DW4 HETEROZYGOUS CHILDREN WITH TYPE-1 (INSULIN-DEPENDENT) DIABETES
EVIDENCE OF AN ACCELERATED B-CELL DESTRUCTION IN HLA-DW3/DW4 HETEROZYGOUS CHILDREN WITH TYPE-1 (INSULIN-DEPENDENT) DIABETES
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DOI：
10.1007/bf00903342
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发表时间：
1986-06-01
期刊：
影响因子：
8.2
通讯作者：
AKERBLOM, HK
中科院分区：
文献类型：
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作者：
KNIP, M;ILONEN, J;AKERBLOM, HK
在144名糖尿病儿童和青少年的横断面系列研究中，以及在44名新诊断的糖尿病受试者的前瞻性系列中，研究了1型(胰岛素依赖型)糖尿病患者残留B细胞功能与特定的人类白细胞抗原之间的可能联系。在横断面研究中，在1980年，人类白细胞抗原-Dw3/Dw4杂合子的平均血清C-肽浓度较低，为0.03。0.01nmol/L(平均值+-扫描电子显微镜)与0.09。+-。0.01nmol/L(p<；0.02)，以及较低的24小时尿C-肽排泄量，0.27。0.06nmol/m2 vs.1.34+-。0.19nmol/m~2(p<；0.05)。此外，Dw3/Dw4杂合子的临床缓解时间较短，为113.+-。47天对203天。+-。22天(p<；0.05)，1980年期间平均糖化血红蛋白水平较高，14.8±-。0.05%对13.7.+-0.2%(p<；0.05)，比没有Dw3/Dw4组合的人高。在前瞻性研究中，Dw3/Dw4杂合子和其他受试者在第一个月的血清C-肽浓度相同。随后，具有Dw3/Dw4组合的受试者的C-Petpide浓度比其他受试者提前2个月开始下降。Dw3/Dw4儿童在21个月时血清C-肽浓度显著降低，0.01。+-。0.01nmol/L vs.0.13+-。0.02nmol/L(p<；0.01)，24月龄为0.03+-。0.01nmol/L vs.0.12.+-。0.02nmol/L(p<；0.05)。我们的观察表明，至少在儿童中存在Dw3/Dw4杂合子，与一种独特的1型糖尿病相关，其特征是B细胞迅速破坏，临床缓解时间短，代谢控制差。这扩大了持续时间短和代谢控制差的问题。这扩大了儿童期1型糖尿病遗传异质性的概念，并可能对该病的病因学、发病机制和自然病史的研究具有重要意义。
The possible association between residual B-cell function and specific HLA antigens in Type 1 (insulin-dependent) diabetes was studied in a cross-sectional series of 144 diabetic children and adolescents, as well as in prospective series of 44 newly diagnosed diabetic subjects who were observed for the initial 2 years of their diabetes. In the cross-sectional study, the HLA-Dw3/Dw4 heterozygotes had a lower mean serum C-peptide concentration during 1980, 0.03 .+-. 0.01 nmol/l (mean .+-. SEM) vs. 0.09 .+-. 0.01 nmol/l (p < 0.02), as well as a lower 24-h urinary C-peptide excretion, 0.27 .+-. 0.06 nmol/m2 vs. 1.34 .+-. 0.19 nmol/m2 (p < 0.05), than the other subjects. In addition, the Dw3/Dw4 heterozygotes had a clinical remission of shorter duration, 113 .+-. 47 days vs. 203 .+-. 22 days (p < 0.05), and a higher mean glycosylated haemoglobin level during 1980, 14.8 .+-. 0.05% vs. 13.7 .+-. 0.2% (p < 0.05), than those without the Dw3/Dw4 combination. In the prospective study the serum C-peptide concentrations were of the same magnitude in the Dw3/Dw4 heterozygotes and the other subjects during the first month. Subsequently the C-petpide concentrations in the subjects with the Dw3/Dw4 combination started to decrease 2 months earlier than in the other subjects. The Dw3/Dw4 children had a significantly lower serum C-peptide concentration at 21 months, 0.01 .+-. 0.01 nmol/l vs. 0.13 .+-. 0.02 nmol/l (p < 0.01), and at 24 months, 0.03 .+-. 0.01 nmol/l vs. 0.12 .+-. 0.02 nmol/l (p < 0.05). Our observations suggest that Dw3/Dw4 heterozygosity is at least in children, associated with a distinct form of Type 1 diabetes characterized by a rapid B-cell destruction, a clinical remission of short duration and poor metabolic control. This expands the short duration and poor metabolic control. This expands the concept of genetic heterogeneity within Type 1 diabetes in childhood, and may have important implications for research on the aetiology, pathogenesis and natural history of the disease.