Preliminary findings in corneal allograft rejection in patients with keratoconus
Preliminary findings in corneal allograft rejection in patients with keratoconus
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DOI：
10.1016/s0002-9394(02)02055-x
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发表时间：
2003-04-01
影响因子：
4.2
通讯作者：
Niederkorn, J
中科院分区：
文献类型：
--
作者：
Hargrave, S;Chu, YL;Niederkorn, J
目的：传统上，角膜异体移植排斥反应被认为是一种T(H)1介导的现象。然而，T(H)2介导的同种异体移植排斥反应在其他移植器官系统中也有报道，包括心脏和肾脏。我们之前报道了一种T(H)2免疫偏倚小鼠模型中T(H)2介导的角膜异体移植排斥反应。在这项研究中，我们试图确定是否有任何证据表明这种形式的角膜移植排斥在人类。设计：采用介入性病例系列的实验研究。方法：回顾性分析1994 ~ 1999年在德克萨斯大学西南医学中心行穿透性角膜移植术的圆锥角膜患者的临床资料。对特应性反应的临床病史给予了仔细的关注。选择特应性患者，因为这些患者已被证明具有“T(H)2免疫偏倚”。观察患者角膜移植排斥率及重复角膜移植次数。实验组包括有异位性和圆锥角膜病史的患者，他们因免疫排斥的角膜移植而至少做过一次重复穿透性角膜移植术。任何有原发性同种异体移植失败证据的患者都被排除在本研究之外。这些患者的组织标本包埋于石蜡中，连续切片，用吉姆萨染色，并进行组织学检查。对照组包括pa，无过敏临床史（因此没有T(H)2免疫偏倚），因Fuch角膜内皮营养不良或无晶状体/假晶状体大疱性角膜病变而接受角膜移植的患者。来自这些对照患者的失败移植物也进行石蜡包埋，连续切片，染色和组织学检查。将人类实验和对照角膜标本与小鼠T(H)2介导的角膜移植排斥反应模型进行比较。简单地说，将全厚度穿透C57BL/6ByJ角膜同种异体移植物移植到Balb/cByJ和Balb/c- ifn - γ (tmlTs) （Balb/c- ifn - γ敲除）小鼠身上。此外，将全厚Balb/cByJ异体角膜移植到C57BL/6ByJ和C57BL/6ByJ- ifn - γ (tmlTs)小鼠身上。计算并比较野生、型和干扰素γ (ifn - γ)敲除宿主之间的同种异体移植排斥率和平均排斥时间。被排斥的同种异体移植物用与人体组织相同的方法进行组织学检查。结果：1994 ~ 1999年共行84例圆锥角膜穿透性角膜移植术。84例患者中有7例排斥角膜移植。在7例排斥异体角膜移植的患者中，4例进行了重复穿透性角膜移植术。在这4例重复角膜异体移植物中，与对照组患者的排斥移植物相比，3例出现嗜酸性粒细胞增多。与不存在T(H)2偏倚的患者相比，特应性圆锥角膜患者在排斥的角膜组织标本中有混合炎性细胞浸润，嗜酸性粒细胞密度显著增加（P = 0.001）。在这些没有T(H)2免疫偏倚的患者中，炎症浸润是单核的。在小鼠模型中，在缺乏ifn - γ（一种关键的T(H)1细胞因子）的情况下，角膜同种异体移植确实会发生排斥反应。组织学上，与野生型动物（“T(H)1小鼠”）相比，这些（“T(H)2小鼠”）的排斥反应的特征是在被排斥的角膜移植床中主要有嗜酸性粒细胞浸润，而野生型动物（“T(H)1小鼠”）在被排斥的角膜移植床中主要有单核浸润。结论：初步研究结果表明，先前存在T(H)2表型的患者的角膜移植排斥反应与TH2介导的角膜移植排斥反应的小鼠模型相似。基于这个小样本，似乎嗜酸性粒细胞可能在这组患者的角膜异体移植排斥反应中起作用。然而，需要进一步的研究来确定这些细胞在同种异体移植排斥反应中的重要性。(C) 2003年由爱思唯尔科学有限公司版权所有。
PURPOSE: Classically, corneal allograft rejection is thought to be a T(H)1-mediated phenomenon. However, T(H)2-mediated allograft rejection has been reported in other transplanted organ systems, including the heart and kidney. We previously reported a form of T(H)2-mediated corneal allograft rejection in a murine model with a T(H)2 immune bias. In this study we sought to determine if there was any evidence for this form of corneal allograft rejection in humans.DESIGN: Experimental study with an interventional case series.METHODS: The clinical records of all keratoconus patients undergoing penetrating keratoplasty at the University of Texas, Southwestern Medical Center from 1994 to 1999 were reviewed. Careful attention was paid to a clinical history of atopy. Atopic patients were selected, because these patients have been shown to have a "T(H)2 immune bias." The corneal graft rejection rate in these patients and the number of repeat corneal trans, plants performed was determined. The experimental group consisted of patients with a clinical history of atopy and keratoconus who had at least one repeat penetrating keratoplasty for an immunologically rejected corneal transplant. Any patient with evidence of primary allograft failure was excluded from this study. Tissue specimens from these patients were embedded in paraffin, serially sectioned, stained with Giemsa stains, and exam, ined histologically. The control group consisted of pa, tients without a clinical history of allergy (and therefore no T(H)2 immune bias) who underwent corneal transplantation for Fuch corneal endothelial dystrophy, or aphakic/pseudophakic bullous keratopathy. Failed grafts from these control patients were also paraffin embedded, serially sectioned, stained, and examined histologically. The human experimental and control corneal specimens were compared with data obtained in a murine model of T(H)2,mediated corneal allograft rejection. Briefly, full, thickness penetrating C57BL/6ByJ corneal allografts were transplanted onto Balb/cByJ and Balb/c-IFN-gamma(tmlTs) (Balb/c-IFN-gamma knockout) mice. Additionally, full-thick- ness Balb/cByJ corneal allografts were transplanted onto C57BL/6ByJ and C57BL/6ByJ-IFN-gamma(tmlTs) mice. Cor, neal allograft rejection rates and mean rejection times were calculated and compared between wild,type and interferon gamma (IFN-gamma) knockout hosts. The rejected allografts were examined histologically by the same meth, ods used in the human tissue.RESULTS: There were 84 penetrating keratoplasties performed from 1994 to 1999 for keratoconus. Seven of these 84 patients rejected their corneal grafts. Of the 7 patients who rejected their corneal allografts, 4 had repeat penetrating keratoplasty. Of these 4 repeat corneal allografts, 3 showed eosinophilia when compared with rejected grafts in control patients. Atopic keratoconus patients had a mixed inflammatory cellular infiltrate in the rejected corneal tissue specimen with a significantly greater density of eosinophils (P =.001) compared with patients who did not have a pre-existing T(H)2 bias. The inflammatory infiltrate in these patients without a T(H)2 immune bias was mononuclear. In the murine model, corneal allograft rejection did occur in the absence of IFN-gamma, a critical T(H)1 cytokine in both fully allogeneic donor-host combinations. Histologically, rejection in these ("T(H)2 mice") was characterized by a predominant eosinophilic infiltrate in the rejected graft bed when compared with wild,type animals ("T(H)1 mice") that had a predominately mononuclear infiltrate in the rejected corneal graft bed.CONCLUSION: Preliminary findings show that corneal allograft rejection in patients with a pre-existing T(H)2 phenotype is similar to what is seen in the murine model of TH2,mediated corneal allograft rejection. Based on this small sample, it appears that eosinophils may play a role in corneal allograft rejection in this group of patients. However, further study is necessary to determine the importance of these cells in allograft rejection. (C) 2003 by Elsevier Science Inc. All rights reserved.