Böhringer D, Schwartzkopff J, Maier P C, Reinhard T
Augenklinik, Universitätsklinik, Killianstrasse 5, Freiburg.
Klin Monbl Augenheilkd. 2013 May;230(5):490-3. doi: 10.1055/s-0032-1328256. Epub 2013 May 21.
The immunological mechanisms of graft rejections after penetrating keratoplasty are largely investigated in rodent models. Here, antigens are predominantly processed by host antigen presenting cells (APCs). For this reason, graft rejections are not primarily triggered by mismatches in the major histocompatibility complex (MHC). Consequently, MHC matching (equivalent of HLA matching) does not robustly prevent immunological graft rejections in mice. This, however, may not apply to humans because anatomy and the clinical picture of immune reactions differ vastly.
Immunological experiments are not feasible in humans for ethical reasons. However, the recent surgical modifications in keratoplasty inadvertently gave rise to several interesting immunological field experiments. We herein discuss the potential insight into human graft rejections from selected clinical observations. On this basis, we have evaluated HLA matching for keratoplasty techniques.
Several clinical observations hint towards an active role of donor-derived APCs in graft rejections after human keratoplasty. Additionally, donor-specific anti-HLA antibodies may play a significant role. On this basis we suggest that HLA matching is potentially beneficial in human keratoplasty in contrast to the situation in mice.
Graft rejections are rarely observed after Descemet membrane keratoplasty (DMEK). For this reason, we do not recommend HLA matching here. The same is true for deep anterior lamellar keratoplasty, where graft rejections can usually be treated well. However, HLA matching is a viable option in penetrating keratoplasty. This is especially true for high-risk eyes.
穿透性角膜移植术后移植物排斥反应的免疫机制主要在啮齿动物模型中进行研究。在此模型中,抗原主要由宿主抗原呈递细胞(APC)处理。因此,移植物排斥反应并非主要由主要组织相容性复合体(MHC)的错配引发。所以,MHC匹配(等同于人类白细胞抗原(HLA)匹配)并不能有力地预防小鼠的免疫性移植物排斥反应。然而,这可能不适用于人类,因为免疫反应的解剖结构和临床表现差异巨大。
出于伦理原因,免疫实验在人体中不可行。然而,最近角膜移植手术的改进无意中引发了一些有趣的免疫领域实验。我们在此讨论从选定的临床观察中对人类移植物排斥反应的潜在见解。在此基础上,我们评估了角膜移植技术中的HLA匹配情况。
一些临床观察表明供体来源的APC在人类角膜移植术后的移植物排斥反应中发挥积极作用。此外,供体特异性抗HLA抗体可能起重要作用。在此基础上,我们认为与小鼠的情况不同,HLA匹配在人类角膜移植中可能有益。
在Descemet膜角膜移植术(DMEK)后很少观察到移植物排斥反应。因此,我们在此不建议进行HLA匹配。对于深前板层角膜移植术也是如此,其移植物排斥反应通常可以得到很好的治疗。然而,HLA匹配在穿透性角膜移植术中是一个可行的选择。对于高危眼尤其如此。