接受胰腺移植的糖尿病患者复发性β细胞破坏的血清学标志物。

Serological markers of recurrent beta cell destruction in diabetic patients undergoing pancreatic transplantation.

作者信息

Thivolet C, Abou-Amara S, Martin X, Lefrancois N, Petruzzo P, McGregor B, Bosshard S, Dubernard J M

机构信息

INSERM 449, Faculty of Medicine RTH Laënnec, Lyon, France.

出版信息

Transplantation. 2000 Jan 15;69(1):99-103. doi: 10.1097/00007890-200001150-00018.

DOI:10.1097/00007890-200001150-00018

PMID:10653387

Abstract

BACKGROUND

Besides alloimmunity to transplanted pancreatic tissue, recurrent autoimmune beta cell destruction is an additional limitation to successful clinical pancreatic allografts in type 1 diabetic patients.

METHODS

We studied the prevalence of autoantibodies to glutamate decarboxylase (GAD) 65 and tyrosine phosphatase (IA-2) in 68 C-peptide-negative diabetic patients receiving pancreatic allografts. Sera from patients were obtained immediately before grafting. A second blood sample was analyzed at the time of graft failure in patients who returned to hyperglycemia and during the same follow-up period in those who experienced a functional pancreatic allograft. Patients were classified according to clinical outcome into chronic graft failure (group A, n=20), acute graft failure and/or arterial thrombosis (n=7), or functional pancreatic graft (group C, n=41). Sera from patients were screened for the presence of specific autoantibodies using an islet cell autoantibody assay, a combi-GAD and IA-2 test, and individual GAD and IA-2 assays.

RESULTS

Patients from group A had significantly higher combi-test values than patients from group C (13+/-16 vs. 4.5+/-12 units, P<0.02) and higher anti-GAD65 antibody (Ab) levels (0.19+/-0.3 vs. 0.04+/-0.13 units, P<0.01) immediately before grafting. After graft failure in group A, both anti-GAD65 and anti-IA-2 Ab levels increased from baseline, but only the increase in anti-IA-2 Ab levels reached statistical significance (0.28+/-0.12 vs. 15+/-34, P=0.03). When compared with group C, patients from group A had higher anti-GAD65 Abs (0.29+/-0.35 vs. 0.05+/-0.16, P<0.001) after graft failure. Interestingly, the number of double-Ab-positive patients rose from 5% to 35% in group A, whereas it remained at 5% in group C. In pancreatic transplants with bladder drainage, the presence of anti-GAD65 and/or anti-IA2 Abs was not associated with a reduction in urinary amylase levels. This suggests that a loss of endocrine function was not associated with exocrine failure in patients from group A.

CONCLUSIONS

We can conclude from the present study that peripheral autoimmune markers are useful in diabetic patients receiving pancreatic allografts.

摘要

背景

除了对移植胰腺组织的同种免疫外，复发性自身免疫性β细胞破坏是1型糖尿病患者临床胰腺移植成功的另一个限制因素。

方法

我们研究了68例接受胰腺移植的C肽阴性糖尿病患者中谷氨酸脱羧酶（GAD）65和酪氨酸磷酸酶（IA-2）自身抗体的患病率。在移植前即刻采集患者血清。对于血糖恢复升高的移植失败患者以及胰腺移植功能正常患者的同一随访期，采集第二份血样进行分析。根据临床结局将患者分为慢性移植失败组（A组，n = 20）、急性移植失败和/或动脉血栓形成组（n = 7）或胰腺移植功能正常组（C组，n = 41）。使用胰岛细胞自身抗体检测、GAD和IA-2联合检测以及单独的GAD和IA-2检测对患者血清进行特异性自身抗体筛查。

结果

A组患者在移植前联合检测值显著高于C组患者（13±16 vs. 4.5±12单位，P<0.02），抗GAD65抗体（Ab）水平也更高（0.19±0.3 vs. 0.04±0.13单位，P<0.01）。A组移植失败后，抗GAD65和抗IA-2 Ab水平均较基线升高，但只有抗IA-2 Ab水平的升高具有统计学意义（0.28±0.12 vs. 15±34，P = 0.03）。与C组相比，A组移植失败后的患者抗GAD65 Abs更高（0.29±0.35 vs. 0.05±0.16，P<0.001）。有趣的是，A组双抗体阳性患者的比例从5%升至35%，而C组仍为5%。在膀胱引流的胰腺移植中，抗GAD65和/或抗IA2 Abs的存在与尿淀粉酶水平降低无关。这表明A组患者内分泌功能丧失与外分泌功能衰竭无关。