1型糖尿病发病前后异常的单核细胞前列腺素合成酶2（PGS2）表达。

Aberrant monocyte prostaglandin synthase 2 (PGS2) expression in type 1 diabetes before and after disease onset.

作者信息

Litherland S A, She J X, Schatz D, Fuller K, Hutson A D, Peng R H, Li Y, Grebe K M, Whittaker D S, Bahjat K, Hopkins D, Fang Q, Spies P D, North K, Wasserfall C, Cook R, Dennis M A, Crockett S, Sleasman J, Kocher J, Muir A, Silverstein J, Atkinson M, Clare-Salzler M J

机构信息

Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Box 100275, JHMHC, Gainesville, Florida 32610, USA.

出版信息

Pediatr Diabetes. 2003 Mar;4(1):10-8. doi: 10.1034/j.1399-5448.2003.00042.x.

DOI:10.1034/j.1399-5448.2003.00042.x

PMID:14655518

Abstract

METHODS

We examined monocyte prostaglandin synthase 2 (PGS2/COX2) expression in individuals at risk for or with type 1 diabetes including: (i) 58 established type 1 and 2 diabetic patients; (ii) 34 autoantibody positive (AA+) children and adults; (iii) 164 infants and young children with insulin-dependent diabetes mellitus (IDDM) susceptibility human leukocyte antigen (HLA) alleles; and (iv) 37 healthy control individuals, over a 5-yr period.

RESULTS

Established type 1 diabetic patients (1 month to 30+ yr post-disease onset) had significantly higher PGS2 expression than healthy controls; by contrast, insulin-treated type 2 diabetic patients had significantly lower PGS2 expression than healthy controls. Longitudinal studies of AA+ subjects at risk for type 1 diabetes indicated that 73% (11/15) of individuals who developed this disease during the study period expressed high levels of PGS2 prior to or after onset. We also found high level PGS2 expression in genetically at-risk infants and young children that correlated with having a first-degree relative with type 1 diabetes, but not with age, gender, or HLA genotype. In this population, high level PGS2 expression coincided with or preceded autoantibody detection in 30% (3/10) of subjects.

CONCLUSIONS

These findings suggest that high level monocyte PGS2 expression, although subject to fluctuation, is present in at-risk subjects at an early age and is maintained during progression to and after type 1 diabetes onset.

摘要

方法

我们检测了1型糖尿病高危个体或1型糖尿病患者的单核细胞前列腺素合成酶2（PGS2/COX2）表达，这些个体包括：（i）58例确诊的1型和2型糖尿病患者；（ii）34例自身抗体阳性（AA+）的儿童和成人；（iii）164例具有胰岛素依赖型糖尿病（IDDM）易感人类白细胞抗原（HLA）等位基因的婴幼儿；以及（iv）37名健康对照个体，研究为期5年。

结果

确诊的1型糖尿病患者（疾病发作后1个月至30多年）的PGS2表达显著高于健康对照；相比之下，接受胰岛素治疗的2型糖尿病患者的PGS2表达显著低于健康对照。对1型糖尿病高危AA+受试者的纵向研究表明，在研究期间患此病的个体中有73%（11/15）在发病前或发病后表达高水平的PGS2。我们还发现，在有1型糖尿病遗传风险的婴幼儿中，PGS2表达水平较高，这与有1型糖尿病的一级亲属有关，但与年龄、性别或HLA基因型无关。在这一人群中，30%（3/10）的受试者中PGS2高水平表达与自身抗体检测同时出现或先于自身抗体检测。