Screening for Insulitis in Adult Autoantibody-Positive Organ Donors

中华首席医学网    2008年05月28日 21:33:12 Wednesday  

 

作者：Peter In't Veld, Dirk Lievens, Joeri De Grijse, Zhidong Ling, Bart Van der Auwera, Miriam Pipeleers-Marichal, Frans Gorus, and Daniel Pipeleers

作者单位：the Diabetes Research Center, Brussels Free University and Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes, Brussels, Belgium

《糖尿病学杂志》2007年9月56卷9期 文章精华

 

【摘要】  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 (aAbs) against islet cell antigens exhibit insulitis and/or a reduced -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 (IA-2As), 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+/CD8+ T-cells and CD68+ macrophages; in one case, it was associated with insulin+ cells that expressed the proliferation 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 -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 -cell proliferation. No decrease in -cell mass was detected in cases with insulitis or in the group of antibody+ subjects.

【关键词】  aAb, autoantibody; GADA, glutamate decarboxylase autoantibody; IAA, insulin autoantibody; IA-2A, insulinoma-associated protein 2 autoantibody; ICA, islet cell antibody; LCA, leukocyte common antigen

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