Department of Surgery, University of Miami School of Medicine, Miami, FL.
Makana Therapeutics, Miami, FL.
Immunohorizons. 2023 Sep 1;7(9):619-625. doi: 10.4049/immunohorizons.2300056.
Organ supply remains inadequate to meet the needs of many patients who could benefit from allotransplantation. Xenotransplantation, the use of animals as organ donors, provides an opportunity to alleviate this challenge. Pigs are widely accepted as the ideal organ donor, but humans and nonhuman primates have strong humoral immune responses to porcine tissue. Although carbohydrate xenoantigens have been studied intensively, the primate Ab response also targets class I and class II swine leukocyte Ags (SLAs). Human Abs that recognize HLAs can cross-react with SLA molecules because epitopes can be shared across species. However, ∼15% of people may also exhibit Abs toward class II SLAs despite lacking Abs that also recognize class II HLAs. Here, we extend these studies to better understand human Ab responses toward class I SLAs. When tested against a panel of 18 unique class I SLA proteins, 14 of 52 sera samples collected from patients in need of an organ transplant contained Abs that bound class I SLAs. Class I SLA-reactive sera may contain IgM only, IgG, only, or IgM and IgG capable of recognizing the pig proteins. The presence of class I HLA-reactive Abs was not essential to generating anti-class I SLA Ig. Last, anti-class I SLA reactivity varied by serum; some recognized a single SLA allele, whereas others recognized multiple class I SLA proteins.
器官供应仍然不足以满足许多可以从同种异体移植中受益的患者的需求。异种移植，即使用动物作为器官供体，为缓解这一挑战提供了机会。猪被广泛认为是理想的器官供体，但人类和非人类灵长类动物对猪组织有强烈的体液免疫反应。尽管碳水化合物异种抗原已被深入研究，但灵长类动物的 Ab 反应也针对 I 类和 II 类猪白细胞抗原（SLA）。能够识别 HLA 的人类 Abs 可以与 SLA 分子发生交叉反应，因为表位可以在物种之间共享。然而，尽管缺乏也能识别 II 类 HLA 的 Abs，仍有约 15%的人可能也会针对 II 类 SLA 产生 Abs。在这里，我们扩展了这些研究以更好地了解人类针对 I 类 SLA 的 Ab 反应。当针对一组 18 种独特的 I 类 SLA 蛋白进行测试时，从需要器官移植的患者中收集的 52 份血清样本中的 14 份含有与 I 类 SLA 结合的 Abs。I 类 SLA 反应性血清可能仅含有 IgM、IgG 或能够识别猪蛋白的 IgM 和 IgG。存在 I 类 HLA 反应性 Abs 并不是产生抗 I 类 SLA Ig 的必要条件。最后，抗 I 类 SLA 的反应性因血清而异；一些识别单个 SLA 等位基因，而另一些则识别多个 I 类 SLA 蛋白。
