Mujtaba Muhammad Ahmad, Fridell Jonathan, Book Benita, Faiz Sara, Sharfuddin Asif, Wiebke Eric, Rigby Mark, Taber Tim
Division of Nephrology/Transplant, Department of Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Division of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Clin Transplant. 2015 Nov;29(11):991-6. doi: 10.1111/ctr.12619. Epub 2015 Oct 22.
Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p < 0.0001), 12 months (p < 0.0001), and from post-6 to post-12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.
再次接触β细胞自身抗原及其在胰腺同种异体移植受者中存在供体特异性抗体(DSA)时的相关性尚不清楚。33名需要进行胰腺移植的患者参加了一项经机构审查委员会(IRB)批准的研究。他们接受了DSA和针对谷氨酸脱羧酶65(GAD65)、胰岛素瘤相关抗原2(IA-2)、胰岛素(微量胰岛素自身抗体[mIAA])和胰岛特异性锌转运体8(ZnT8)的β细胞自身抗体(BCAA)水平的前瞻性监测。25名(75.7%)患者移植前存在BCAA。20名患者有单一抗体(mIAA n = 15,GAD65 n = 5);5名患者有两种或更多种BCAA(GAD65 + mIAA n = 2,GAD65 + mIAA + IA-2 n = 2,GA65 + mIAA + IA-2 + ZnT8 = 1)。在移植前与移植后6个月或12个月时,未观察到GAD-65(p > 0.29)、IA-2(p > 0.16)和ZnT8(p > 0.07)水平有变化。mIAA在移植后6个月(p < 0.0001)、12个月(p < 0.0001)以及移植后6个月至12个月(p = 0.0002)均出现下降。1年时未观察到新的BCAA。7名(21.0%)患者出现了新发DSA。有BCAA的患者中DSA发生率为24%,无BCAA的患者中DSA发生率为25%(p = 0.69)。直至最后一次随访(3年),有BCAA与无BCAA的患者以及有BCAA + DSA与无BCAA + DSA的患者的胰腺同种异体移植功能相当。胰腺移植导致再次接触β细胞自身抗原可能不会导致BCAA水平升高或新的BCAA产生,也不会导致胰腺同种异体移植功能障碍。