补体结合的供者特异性抗体对稳定期肾移植受者预后影响的临床总结

doi:10.3877/cma.j.issn.1674-3903.2025.01.010

目的

探讨新生供者特异性抗体(dnDSA)及补体(C1q和C3d)结合的dnDSA对移植肾功能稳定受者长期生存的影响。

方法

回顾性分析2009年12月至2015年5月在山西省第二人民医院首次实施肾移植且接受抗HLA抗体检测的48例受者临床资料,根据抗HLA抗体检测结果及供者高分位点将其为dnDSA组、非供者特异性抗体(NDSA)组及抗HLA抗体阴性组。根据补体检测结果将dnDSA组和NDSA组受者分为C1q⁺组、C1q⁺C3d⁺组和C1q^-C3d^-组。分析受者肾功能、受者/移植肾存活率、移植肾失功和移植肾急性排斥反应等指标。多组间计量资料比较采用单因素方差分析或Kruskal-Wallis H检验；组间计数资料比较采用χ²检验或Fisher确切概率法。采用Kaplan-Meier法绘制生存曲线,并通过log-rank检验进行比较。P＜0.05为差异有统计学意义。

结果

dnDSA组(n=9例)、NDSA(n=15例)及抗HLA抗体阴性组(n=24例)受者行抗HLA抗体检测时移植时间分别为108.0(69.0～130.5)个月、42.0(2.0～78.0)个月和40.0(5.3～77.3)个月,HLA-Ⅱ类抗体MFI值分别为29 534(11 761～23 961)、3 239(1 699～12 277)和411(185～1 297),差异均有统计学意义(H=7.88和35.78,P均＜0.05)。dnDSA组C1q⁺C3d⁺受者比例高于NDSA组,C1q^-C3d^-受者比例低于NDSA组,差异均有统计学意义(P均＜0.05)。随访截至2024年6月,dnDSA组、NDSA组和抗HLA抗体阴性组移植肾失功比例分别为3/9、1/15和2/24,差异无统计学意义(P＞0.05)。dnDSA组受者移植后15年移植肾/受者生存率分别62.2%/88.9%,NDSA组分别为75.0%/100%,抗HLA抗体阴性组分别91.5%/100%,差异均无统计学意义(χ²=2.07和1.67,P均＞0.05)。C1q⁺组、C1q⁺C3d⁺组和C1q^-C3d^-组受者移植肾急性排斥反应和移植肾失功发生比例均依次为0、4/11、0,差异均有统计学意义(P均＜0.05)。

结论

dnDSA影响稳定期肾移植受者预后,DSA与补体C1q、C3d联合检测可能对预测移植肾长期存活并指导临床干预具有重要价值。

关键词: 供者特异性抗体, 补体, 肾移植, 抗体介导排斥反应

Objective

To investigate the effect of denovo donor-specific antibody (dnDSA)and complement (C1q and C3d)-binding dnDSA on the long-term survival of stable kidney transplant recipients.

Methods

A total of 48 kidney recipients who underwent kidney transplantation in the Second People's Hospital of Shanxi Province from December 2009 to May 2015 were included, whose kidney function was stable at the time of admission. The HLA antibody test was completed in 2015.According to the HLA antibody test results and the HLA alleles of the donors, the 48 recipients were divided into the dnDSA group, the non-DSA (NDSA) group, and the anti-HLA antibody-negative group. The recipients in the dnDSA group and the NDSA group were further divided into the C1q⁺group, the C1q⁺C3d⁺

group, and the C1q^-C3dgroup based on the complement test results. The kidney function, recipient/graft survival rate, graft failure, and acute rejection were analyzed. The comparison of quantitative data among multiple groups was conducted using one-way analysis of variance or Kruskal-Wallis H test； the comparison of count data between groups was conducted using the chi-square test or Fisher's exact probability method. The survival curve was plotted using the Kaplan-Meier method, and the log-rank test was used for comparison. P＜0.05 was considered statistically significant.

Results

For the recipients in the dnDSA group (n=9), NDSA group (n=15 ), and the anti-HLA antibody-negative group (n=24), the transplantation time was 108.0 (69.0-130.5),42.0 (2.0-78.0), and 40.0 (5.3-77.3) months. The MFI values of HLA-Ⅱ were 29 534 (11 761-23 961), 3 239 (1 699-12 277), and 411 (185-1 297) respectively. The differences were all statistically significant (H=7.88 and 35.78, all P＜0.05). The proportion of C1q⁺C3d⁺recipients in the dnDSA group was higher than that in the NDSA group (P＜0.05)； the proportion of C1q^-C3drecipients in the NDSA group was higher than that in the dnDSA group (P＜0.05). Up to June 2024,the proportions of graft loss in the dnDSA group, NDSA group, and anti-HLA antibody negative group were 3/9, 1/15 and 2/24, with no statistical difference (P＞0.05). The 15-year graft/recipient survival rates were 62.2%/88.9% (dnDSA group), 75.0%/100% (NDSA group), and 91.5%/100%(anti-HLA antibody-negative group), with no statistical significance (χ²=2.07 and 1.67, all P＞0.05). The incidence of acute rejection in C1q⁺group, C1q⁺C3d⁺ group and C1q^-C3d^-group was 0,4/11 and 0. The difference was also statistically significant (P＜0.05). The incidence of graft loss were 0, 4/11 and 0, and the difference was statistically significant (P＜0.05).

Conclusions

dnDSA affects the prognosis of kidney transplant recipients in a stable condition. The combined detection of DSA with C1q and C3d may have important value in predicting the long-term survival of transplanted kidney and guiding the clinical intervention.

Key words: Donor-specific antibody, Complement, Kidney transplantation, Antibodymediated rejection

表1 dnDSA、NDSA和抗HLA抗体阴性组肾移植受者抗HLA抗体检测时一般资料比较

组别	例数	年龄(岁, $\overset{ˉ}{x}$ ±s)	性别(例,男/ 女)	BMI(kg/ m², $\overset{ˉ}{x}$ ±s)	原发病(例,肾小球肾炎/ 其他)	移植时间[月,M（P₂₅，P₇₅）]
dnDSA 组	9	32±11	5/4	19. 6±3. 1	9/0	108. 0(69. 0～130. 5)
NDSA 组	15	40± 9	7/8	20. 9±3. 0	12/3	42. 0( 2. 0～ 78. 0)^a
抗HLA 抗体阴性组	24	35±10	16/8	21. 2±4. 3	23/1	40. 0( 5. 3～ 77. 3)^a
F / χ ² / H 值	-	2. 15	1. 61	0. 59	3. 01	7. 88
P值	-	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＜0. 05
组别	例数	血清肌酐(μmol/ L, $\overset{ˉ}{x}$ ±s)	eGFR[mL·min^-1·(1. 73 m²)^-1, $\overset{ˉ}{x}$ ±s]	HLA-Ⅰ类 MFI 值[M（P₂₅，P₇₅）]	HLA-Ⅱ类MFI 值[M（P₂₅，P₇₅）]
dnDSA 组	9	102. 3±32. 1	71. 1±25. 3	1 173(931～2 765)	29 534(11 761～23 961)
NDSA 组	15	87. 5±18. 4	72. 9±17. 0	749(648～1 342)	3 239( 1 699～12 277)^a
抗HLA 抗体阴性组	24	88. 8±20. 8	74. 5±17. 3	298(116～ 765)	411( 185～ 1 297)^a
F / χ ² / H 值	-	1. 13	1. 60	2. 86	35. 78
P值	-	＞0. 05	＞0. 05	＞0. 05	＜0. 05
组别	例数	捐献类型(例,活体肾移植)	维持期免疫抑制方案(例)
组别	例数	捐献类型(例,活体肾移植)	他克莫司+霉酚酸类药物+糖皮质激素	环孢素+霉酚酸类药物+糖皮质激素	他克莫司+咪唑立宾+糖皮质激素
dnDSA 组	9	1	4	2	3
NDSA 组	15	2	9	2	4
抗HLA 抗体阴性组	24	1	12	3	9
F / χ ² / H 值	-	2. 06	0. 69	0. 81	0. 54
P值	-	＞0. 05	＞0. 05	＞0. 05	＞0. 05

表1 dnDSA、NDSA和抗HLA抗体阴性组肾移植受者抗HLA抗体检测时一般资料比较

组别	例数	年龄(岁, $\overset{ˉ}{x}$ ±s)	性别(例,男/ 女)	BMI(kg/ m², $\overset{ˉ}{x}$ ±s)	原发病(例,肾小球肾炎/ 其他)	移植时间[月,M（P₂₅，P₇₅）]
dnDSA 组	9	32±11	5/4	19. 6±3. 1	9/0	108. 0(69. 0～130. 5)
NDSA 组	15	40± 9	7/8	20. 9±3. 0	12/3	42. 0( 2. 0～ 78. 0)^a
抗HLA 抗体阴性组	24	35±10	16/8	21. 2±4. 3	23/1	40. 0( 5. 3～ 77. 3)^a
F / χ ² / H 值	-	2. 15	1. 61	0. 59	3. 01	7. 88
P值	-	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＜0. 05
组别	例数	血清肌酐(μmol/ L, $\overset{ˉ}{x}$ ±s)	eGFR[mL·min^-1·(1. 73 m²)^-1, $\overset{ˉ}{x}$ ±s]	HLA-Ⅰ类 MFI 值[M（P₂₅，P₇₅）]	HLA-Ⅱ类MFI 值[M（P₂₅，P₇₅）]
dnDSA 组	9	102. 3±32. 1	71. 1±25. 3	1 173(931～2 765)	29 534(11 761～23 961)
NDSA 组	15	87. 5±18. 4	72. 9±17. 0	749(648～1 342)	3 239( 1 699～12 277)^a
抗HLA 抗体阴性组	24	88. 8±20. 8	74. 5±17. 3	298(116～ 765)	411( 185～ 1 297)^a
F / χ ² / H 值	-	1. 13	1. 60	2. 86	35. 78
P值	-	＞0. 05	＞0. 05	＞0. 05	＜0. 05
组别	例数	捐献类型(例,活体肾移植)	维持期免疫抑制方案(例)
组别	例数	捐献类型(例,活体肾移植)	他克莫司+霉酚酸类药物+糖皮质激素	环孢素+霉酚酸类药物+糖皮质激素	他克莫司+咪唑立宾+糖皮质激素
dnDSA 组	9	1	4	2	3
NDSA 组	15	2	9	2	4
抗HLA 抗体阴性组	24	1	12	3	9
F / χ ² / H 值	-	2. 06	0. 69	0. 81	0. 54
P值	-	＞0. 05	＞0. 05	＞0. 05	＞0. 05

表2 dnDSA、NDSA和抗HLA抗体阴性组肾移植受者抗HLA抗体检测后不同时间肾功能比较(±s)

组别	例数	血清肌酐(μmol/ L)				eGFR[mL·min^-1·(1. 73 m²)^-1]
组别	例数	1 年	3 年	5 年	9 年	1 年	3 年	5 年	9 年
dnDSA 组	9	105. 4±36. 3	101. 0±30. 6	106. 7±37. 4	109. 5±19. 8	65. 3±27. 7	67. 2±23. 1	65. 4±28. 2	58. 5±21. 9
NDSA 组	15	89. 2±18. 8	90. 4±26. 8	93. 1±36. 1	94. 8±27. 2	98. 4±78. 9	83. 4±24. 2	77. 2±23. 2	69. 5±21. 1
抗HLA 抗体阴性组	24	94. 4±24. 8	90. 1±26. 8	91. 7±18. 1	92. 6±22. 4	76. 4±19. 5	83. 4±20. 3	80. 6±17. 3	76. 3±17. 4
F值	-	1. 13	0. 60	0. 77	0. 83	1. 60	1. 80	1. 35	1. 59
P值	-	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＞0. 05

表2 dnDSA、NDSA和抗HLA抗体阴性组肾移植受者抗HLA抗体检测后不同时间肾功能比较(±s)

组别	例数	血清肌酐(μmol/ L)				eGFR[mL·min^-1·(1. 73 m²)^-1]
组别	例数	1 年	3 年	5 年	9 年	1 年	3 年	5 年	9 年
dnDSA 组	9	105. 4±36. 3	101. 0±30. 6	106. 7±37. 4	109. 5±19. 8	65. 3±27. 7	67. 2±23. 1	65. 4±28. 2	58. 5±21. 9
NDSA 组	15	89. 2±18. 8	90. 4±26. 8	93. 1±36. 1	94. 8±27. 2	98. 4±78. 9	83. 4±24. 2	77. 2±23. 2	69. 5±21. 1
抗HLA 抗体阴性组	24	94. 4±24. 8	90. 1±26. 8	91. 7±18. 1	92. 6±22. 4	76. 4±19. 5	83. 4±20. 3	80. 6±17. 3	76. 3±17. 4
F值	-	1. 13	0. 60	0. 77	0. 83	1. 60	1. 80	1. 35	1. 59
P值	-	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＞0. 05	＞0. 05

图1 dnDSA、NDSA和抗HLA抗体阴性组移植肾/受者生存曲线注： a.移植肾术后生存曲线； b.肾移植受者术后生存曲线； dnDSA.新生供者特异性抗体； NDSA.非供者特异性抗体

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[15]	唐敏英, 邬绿莹, 陈津, 路君, 吴仲秋. 肾移植术后BKV 肾病免疫细胞浸润及关键基因分析[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(01): 12-19.

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A clinical summary on the complement-binging donor-specific antibody on prognosis in stable kidney transplant recipients

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A clinical summary on the complement-binging donor-specific antibody on prognosis in stable kidney transplant recipients