Incidence of serum antibodies to xenoantigens on triple-knockout pig cells in different human groups.

IF 3.3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Xenotransplantation Pub Date : 2024-03-01 Epub Date: 2023-08-02 DOI:10.1111/xen.12818
Songzhe He, Tao Li, Hao Feng, Jiaxiang Du, David K C Cooper, Hidetaka Hara, Hongtao Jiang, Dengke Pan, Gang Chen, Yi Wang
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引用次数: 0

Abstract

Background: Xenoantigens other than Gal, Neu5Gc, and Sda may be playing a role in pig graft rejection. We investigated the incidence of antibodies to unknown pig xenoantigen in different human groups.

Methods: We collected blood from TKO/hCD55 pigs (n = 3), and isolated PBMCs and RBCs. Serum samples were collected from (i) healthy human volunteers (n = 43), (ii) patients with end-stage renal disease (ESRD) (n = 87), (iii) the same patients after kidney allotransplantation (n = 50), and (iv) renal allotransplant recipients experiencing T cell-mediated rejection (allo-TCMR, n = 10). The sera were initially incubated with TKO/hCD55 pRBCs (1 × 108 cells) for 1 h to absorb anti-pig antibodies (except against SLA and possibly other antigens not expressed on pRBCs) and then the serum (absorbed or unabsorbed) was tested for antibody binding and complement-dependent cytotoxicity (CDC) to TKO/hCD55 pig PBMCs.

Results: A significant reduction in IgM/IgG binding and CDC was observed in the absorbed sera. Serum obtained before and after renal allotransplantation showed no significant difference in IgM or IgG binding to, or in CDC of, TKO/hCD55 pig cells. IgM antibodies (but rarely IgG) against unknown xenoantigens expressed on TKO/hCD55 PBMCs, possibly against swine leukocyte antigens, were documented in healthy humans, patients with ESRD, and those with renal allografts undergoing acute T cell rejection. IgM (but not CDC) was higher in patients experiencing allo-TCMR.

Conclusion: Human sera contain IgM antibodies against unknown pig xenoantigens expressed on TKO/hCD55 pPBMCs. Although not confirmed in the present study, the targets for these antibodies may include swine leukocyte antigens.

不同人类群体中三重基因敲除猪细胞上的异抗原血清抗体的发生率。
背景:除 Gal、Neu5Gc 和 Sda 外,其他异抗原可能在猪移植物排斥反应中发挥作用。我们调查了不同人类群体中未知猪异抗原抗体的发生率:我们采集了 TKO/hCD55 猪(n = 3)的血液,并分离了 PBMC 和 RBC。血清样本的采集对象包括:(i) 健康的人类志愿者(43 人);(ii) 终末期肾病(ESRD)患者(87 人);(iii) 肾脏异体移植后的相同患者(50 人);(iv) 出现 T 细胞介导的排斥反应的肾脏异体移植受者(allo-TCMR,10 人)。首先将血清与 TKO/hCD55 pRBCs(1 × 108 个细胞)孵育 1 小时以吸收抗猪抗体(针对 SLA 和可能针对 pRBCs 上未表达的其他抗原的抗体除外),然后检测血清(已吸收或未吸收)与 TKO/hCD55 猪 PBMCs 的抗体结合力和补体依赖性细胞毒性(CDC):结果:在吸收的血清中观察到 IgM/IgG 结合率和 CDC 明显降低。肾脏同种异体移植前后获得的血清显示,TKO/hCD55 猪细胞的 IgM 或 IgG 结合力或 CDC 没有明显差异。在健康人、ESRD 患者和发生急性 T 细胞排斥反应的肾脏异体移植患者中,发现了针对 TKO/hCD55 PBMC 上表达的未知异抗原(可能是针对猪白细胞抗原)的 IgM 抗体(但很少有 IgG)。IgM(而非 CDC)在发生异体肾移植 T 细胞排斥反应的患者中更高:结论:人类血清中含有针对在 TKO/hCD55 pPBMCs 上表达的未知猪异抗原的 IgM 抗体。结论:人类血清中含有针对在 TKO/hCD55 pPBMCs 上表达的未知猪异抗原的 IgM 抗体。尽管本研究未证实,但这些抗体的靶标可能包括猪白细胞抗原。
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来源期刊
Xenotransplantation
Xenotransplantation 医学-医学:研究与实验
CiteScore
6.80
自引率
15.40%
发文量
58
审稿时长
>12 weeks
期刊介绍: Xenotransplantation provides its readership with rapid communication of new findings in the field of organ and tissue transplantation across species barriers.The journal is not only of interest to those whose primary area is xenotransplantation, but also to veterinarians, microbiologists and geneticists. It also investigates and reports on the controversial theological, ethical, legal and psychological implications of xenotransplantation.
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