Jordan S C, Vo A, Bunnapradist S, Toyoda M, Peng A, Puliyanda D, Kamil E, Tyan D
Renal Transplant Program, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Transplantation. 2003 Aug 27;76(4):631-6. doi: 10.1097/01.TP.0000080685.31697.FC.
Sensitization to human leukocyte antigens (HLA) is a significant barrier to transplantation. Currently, no proven therapy exists to improve access to transplantation for highly sensitized patients. Here, we report a novel approach using intravenous immune globulin to modulate anti-HLA antibody and improve the chances for successful transplantation.
Forty-five highly HLA-sensitized patients presented as candidates for living-donor kidney transplantation (n=28), cadaveric kidney transplantation (n=15), or heart transplantation (n=2). All patients had a positive CDC crossmatch (CMX) with their donors. In living-donor recipients, intravenous immune globulin (IVIG) was added to the CMX evaluation to determine whether blocking antibodies present in IVIG could inhibit cytotoxicity. For those who showed in vitro inhibition with IVIG (n=26), IVIG was administered (usually as a single dose, 2 g/kg) and the CDC CMX was repeated against the prospective donor immediately after IVIG infusion. If negative, the patient underwent transplantation with their living-donor kidney within 24 to 72 hr. A similar but modified protocol was performed for cadaver donor candidates, all of whom were highly sensitized and had had CMX positivity with multiple donors, negating transplantation. Reductions in CMX positivity, posttransplantation serum creatinine level, number and severity of rejection episodes, and patient and graft survival rates were determined.
Forty-two patients underwent transplantation. IVIG treatment completely abrogated the donor-specific CMXs in 35 of 42 patients. In the remaining 7 patients, the CDC CMX was inhibited, but flow cytometry CMXs remained positive. A total of 13 (31%) of 42 recipients developed rejection episodes 3 to 49 days after transplantation. Three grafts (7%) were lost to rejection. Mean serum creatinine level at 24 months was 1.4+/-0.4 mg/dL. Patient and graft survival rates were 97.6% and 89.1%, respectively, at 24 months.
The in vitro IVIG CMX technique predicts the ability of IVIG to reduce anti-HLA antibody levels in highly sensitized patients. Subsequent in vivo IVIG treatment of responders eliminates the positive CDC CMX and allows for successful transplantation. Thus a positive CMX result is not necessarily a contraindication for transplantation and allows access to transplantation for patients for whom it was previously contraindicated.
对人类白细胞抗原（HLA）致敏是移植的一个重大障碍。目前，尚无经证实的疗法可改善高度致敏患者的移植机会。在此，我们报告一种使用静脉注射免疫球蛋白来调节抗HLA抗体并提高成功移植几率的新方法。
45例高度HLA致敏患者作为活体供肾移植（n = 28）、尸体供肾移植（n = 15）或心脏移植（n = 2）的候选者。所有患者与其供者的补体依赖细胞毒交叉配型（CMX）均为阳性。在活体供肾受者中，将静脉注射免疫球蛋白（IVIG）添加到CMX评估中，以确定IVIG中存在的封闭抗体是否能抑制细胞毒性。对于那些在体外显示IVIG抑制作用的患者（n = 26），给予IVIG（通常为单次剂量，2 g/kg），并在IVIG输注后立即针对预期供者重复进行补体依赖细胞毒交叉配型（CDC CMX）检测。如果结果为阴性，患者在24至72小时内接受活体供肾移植。对尸体供肾候选者采用了类似但经过修改的方案，他们均为高度致敏且与多个供者的CMX检测呈阳性，因而无法进行移植。测定了CMX阳性率的降低、移植后血清肌酐水平、排斥反应的次数和严重程度以及患者和移植物的存活率。
42例患者接受了移植。IVIG治疗使42例患者中的35例供者特异性CMX完全消除。在其余7例患者中，补体依赖细胞毒交叉配型（CDC CMX）受到抑制，但流式细胞术交叉配型仍为阳性。42例受者中有13例（31%）在移植后3至49天发生排斥反应。3例移植物（7%）因排斥反应而丢失。24个月时的平均血清肌酐水平为1.4±0.4 mg/dL。24个月时患者和移植物的存活率分别为97.6%和89.1%。
体外IVIG CMX技术可预测IVIG降低高度致敏患者抗HLA抗体水平的能力。随后对有反应者进行体内IVIG治疗可消除阳性的补体依赖细胞毒交叉配型（CDC CMX），并实现成功移植。因此，阳性的CMX结果不一定是移植的禁忌证，它使之前因该原因而被禁忌的患者能够获得移植机会。
