Service de Chirurgie Digestive, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, CHU Rennes, Univ Rennes, Rennes, France.
Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Univ Rennes, Rennes, France.
PLoS One. 2023 Mar 10;18(3):e0282736. doi: 10.1371/journal.pone.0282736. eCollection 2023.
Graft rejection is a critical risk in solid-organ transplantation. To decrease such risk, an understanding of the factors involved in low immunogenicity of liver allografts could potentially make it possible to transfer this tolerogenic property to other transplanted organs. HLA-G, a natural physiological molecule belonging to the Human Leukocyte Antigen class (HLA) Ib family that induces tolerance, is associated with fewer rejections in solid-organ transplantation. In contrast to HLA-G, HLA antigen incompatibilities between donor and recipient can lead to rejection, except in liver transplantation. We compared HLA-G plasma levels and the presence of anti-HLA antibodies before and after LT to understand the low immunogenicity of the liver. We conducted a large prospective study that included 118 patients on HLA-G plasma levels during a 12-month follow-up and compared them to the status of anti-HLA antibodies. HLA-G plasma levels were evaluated by ELISA at seven defined pre- and post-LT time points. HLA-G plasma levels were stable over time pre-LT and were not associated with patient characteristics. The level increased until the third month post-LT, before decreasing to a level comparable to that of the pre-LT period at one year of follow-up. Such evolution was independent of biological markers and immunosuppressive treatment, except with glucocorticoids. An HLA-G plasma level ≤ 50 ng/ml on day 8 after LT was significantly associated with a higher rejection risk. We also observed a higher percentage of rejection in the presence of donor specific anti-HLA antibodies (DSA) and an association between the increase in HLA-G plasma levels at three months and the absence of DSA. The low immunogenicity of liver allografts could be related to early elevated levels of HLA-G, which lead, in turn, to a decrease in anti-HLA antibodies, opening potential new therapeutic strategies using synthetic HLA-G proteins.
移植物排斥是实体器官移植中的一个关键风险。为了降低这种风险，了解肝移植低免疫原性相关的因素，可能会使我们将这种耐受特性转移到其他移植器官上成为可能。HLA-G 是一种天然的生理分子，属于人类白细胞抗原（HLA）Ib 家族，能够诱导耐受，与实体器官移植中的排斥反应较少有关。与 HLA-G 相反，供体和受体之间的 HLA 抗原不相容性可导致排斥反应，肝移植除外。我们比较了 LT 前后 HLA-G 血浆水平和抗 HLA 抗体的存在，以了解肝脏的低免疫原性。我们进行了一项大型前瞻性研究，该研究纳入了 118 例患者，在 12 个月的随访期间对其 HLA-G 血浆水平进行了比较，并与抗 HLA 抗体的状态进行了比较。通过 ELISA 在七个预先和 LT 后的时间点评估 HLA-G 血浆水平。LT 前 HLA-G 血浆水平随时间保持稳定，与患者特征无关。水平在 LT 后第三个月前增加，然后在一年随访时降低至与 LT 前水平相当。这种演变与生物标志物和免疫抑制治疗无关，除了糖皮质激素。LT 后第 8 天 HLA-G 血浆水平≤50ng/ml 与更高的排斥风险显著相关。我们还观察到在存在供体特异性抗 HLA 抗体（DSA）时排斥反应的百分比更高，以及在三个月时 HLA-G 血浆水平增加与 DSA 缺失之间的关联。肝移植低免疫原性可能与早期 HLA-G 水平升高有关，这反过来又导致抗 HLA 抗体减少，为使用合成 HLA-G 蛋白提供了潜在的新治疗策略。
