Patients on the Transplant Waiting List Have Anti-Swine Leukocyte Antigen Class I Antibodies.
Patients on the Transplant Waiting List Have Anti-Swine Leukocyte Antigen Class I Antibodies.
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DOI：
10.4049/immunohorizons.2300056
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发表时间：
2023-09-01
期刊：
影响因子：
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通讯作者：
Tector AJ
中科院分区：
文献类型：
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作者：
Wang ZY;Reyes L;Estrada J;Burlak C;Gennuso VN;Tector MO;Ho S;Tector M;Tector AJ
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。利用动物作为器官供体的异种移植为缓解这一挑战提供了机会。猪被广泛接受为理想的器官供体，但人类和非人灵长类动物对猪组织有强烈的体液免疫反应。虽然碳水化合物异种抗原已被深入研究，灵长类动物Ab反应也靶向I类和II类猪白细胞抗原（SLA）。识别HLA的人Ab可以与SLA分子交叉反应，因为表位可以在物种间共享。然而，大约15%的人也可能表现出对II类SLA的抗体，尽管缺乏也识别II类HLA的抗体。在这里，我们扩展这些研究，以更好地了解人类抗体对I类SLA的反应。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收集的52份血清样品中有14份含有结合I类SLA的Ab。I类SLA反应性血清可仅含有IgM、仅含有IgG或含有能够识别猪蛋白的IgM和IgG。I类HLA反应性Ab的存在对于产生抗I类SLA IG不是必需的。最后，抗I类SLA的反应性不同的血清，一些承认一个单一的SLA等位基因，而其他人承认多个I类SLA蛋白。
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.