对非遗传母体HLA抗原的耐受性对同胞供体肾移植存活的影响。

The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors.

作者信息

Burlingham W J, Grailer A P, Heisey D M, Claas F H, Norman D, Mohanakumar T, Brennan D C, de Fijter H, van Gelder T, Pirsch J D, Sollinger H W, Bean M A

机构信息

Department of Surgery, University of Wisconsin, Madison 53792, USA.

出版信息

N Engl J Med. 1998 Dec 3;339(23):1657-64. doi: 10.1056/NEJM199812033392302.

DOI:10.1056/NEJM199812033392302

PMID:9834302

Abstract

BACKGROUND

During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors.

METHODS

We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data.

RESULTS

In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient.

CONCLUSIONS

In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.

摘要

背景

在怀孕和哺乳期间，婴儿发育中的免疫系统会密切接触母亲的抗原。为了确定这种接触对成年后接受同种异体移植的患者是否具有临床益处，我们分析了来自同胞供体的初次肾移植结果。

方法

我们回顾性研究了1966年至1996年间在9个中心接受肾移植的205例患者的移植物存活情况和排斥反应发作情况，这些患者的同胞供体携带受者未遗传的母源或父源HLA抗原。通过分析家族HLA分型数据对同胞供体进行分类。

结果

在多中心分析中，接受表达受者未遗传的母源HLA抗原的同胞肾脏移植的患者，其移植后5年和10年的移植物存活率高于接受表达受者未遗传的父源HLA抗原的同胞肾脏移植的患者（5年时分别为86%对67%，10年时分别为77%对49%，两者P均=0.006）。矛盾的是，前一组早期排斥反应的发生率较高，这表明胎儿和新生儿接触母源抗原会导致免疫致敏。移植前输注供体血液可降低急性排斥反应的发生率，同时保留对未遗传的母源抗原的耐受性对移植物存活的有益作用。自1986年以来，新的免疫抑制药物减少了表达受者未遗传的母源HLA抗原的移植物的短期存活优势，但未减少长期存活优势。