Screening for insulitis in adult autoantibody-positive organ donors
Screening for insulitis in adult autoantibody-positive organ donors
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DOI：
10.2337/db07-0416
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发表时间：
2007-09-01
期刊：
影响因子：
7.7
通讯作者：
Pipeleers, Daniel
中科院分区：
文献类型：
--
作者：
In't Veld, Peter;Lievens, Dirk;Pipeleers, Daniel
针对胰岛细胞抗原的抗体被用作1型糖尿病的预测标志物，但尚不清楚它们是否反映了胰岛组织中正在进行的自身免疫过程。我们研究了来自对胰岛细胞抗原的自身抗体（&Abs）呈阳性的成年供体的器官是否表现出胰岛炎和/或减少的P细胞质量。分析了来自1，507名器官供体（年龄25-60岁）的血清中的胰岛细胞抗体（ICA）、谷氨酸脱羧酶aAb（GADA）、胰岛素瘤相关蛋白2 aAb（IA 2As）和胰岛素aAb。检查来自62名aAb（+）供体（4.1%）和匹配对照的组织是否存在胰岛炎和胰岛素（+）细胞的相对面积。在2例病例中检测到胰岛炎;在3%和9%的胰岛中发现，由CD 3（+）/CDS+ T细胞和CD 68（+）巨噬细胞组成;在1例病例中，与表达增殖标记物Ki 67的胰岛素（+）细胞相关。两名受试者均属于伊卡、GADA和IA-2-Ab阳性以及易感HLA-DQ基因型的三名供体亚组。aAb（+）和aAb（-）供体的相对β细胞面积比较未显示显著差异。胰岛炎见于至少3种抗体的3例病例中的2例，但在其他59例抗体（+）受试者或62例匹配对照中均未发现。仅在< 10%的胰岛中检测到，其中一些呈现P细胞增殖的迹象。在胰岛炎病例或抗体（+）受试者组中，未检测到P细胞群减少。
Antibodies against islet cell antigens are used as predictive markers of type 1 diabetes, but it is unknown whether they reflect an ongoing autoimmune process in islet tissue. We investigated whether organs from adult donors that are positive for autoantibodies (&Abs) against islet cell antigens exhibit insulitis and/or a reduced P-cell mass. Serum from 1,507 organ donors (age 25-60 years) was analyzed for islet cell antibodies (ICAs), glutamate decarboxylase aAbs (GADAs), insulinoma-associated protein 2 aAbs (IA2As), and insulin aAbs. Tissue from the 62 aAb(+) donors (4.1%) and from matched controls was examined for the presence of insulitis and for the relative area of insulin(+) cells. Insulitis was detected in two cases; it was found in 3 and 9% of the islets and consisted of CD3(+)/CDS+ T-cells and CD68(+) macrophages; in one case, it was associated with insulin(+) cells that expressed the proliferatiori marker Ki67. Both subjects belonged to the subgroup of three donors with positivity for ICA, GADA, and IA-2-Ab and for the susceptible HLA-DQ genotype. Comparison of relative beta-cell area in aAb(+) and aAb(-) donors did not show a significant difference. Insulitis was found in two of the three cases that presented at least three aAbs but in none of the other 59 antibody(+) subjects or 62 matched controls. It was only detected in < 10% of the islets, some of which presented signs of P-cell proliferation. No decrease in P-cell mass was detected in cases with insulitis or in the group of antibody(+) subjects.