Abstract

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.

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