补体裂解片断C4d在移植肾急性排斥反应中的临床意义

Clinical significance of complement split product C4d deposition in peritubular capillaries in acute renal allograft rejection

目的探讨肾小管周围毛细血管补体裂解片断(C4d)沉积在移植肾急性排斥反应中的临床意义。方法对肾移植后发生急性排斥反应的78例受者进行移植肾活体穿刺检查,共获取移植肾活检穿刺标本86份。根据Banff97病理分型将86份活检标本分为BanffⅠ型32份,Ⅱ型51份,Ⅲ型3份。应用免疫组织化学法检测出86份标本中有30份出现肾小管周围毛细血管C4d沉积,阳性率为34.9%。分析C4d阳性其与Banff97分型、术前一般情况、抗排斥治疗、移植肾功能及移植肾预后的关系。结果BanffⅠ和Ⅱ型受者移植肾中C4d阳性率分别为21.9%和39.2%,两者相比差异无统计学意义(P=0.101)。有妊娠史、术前群体反应性抗体(PRA)>30%和再次移植的受者C4d阳性率较高。C4d阳性的受者发生排斥反应时血肌酐较阴性受者高,分别为(312.56±196.26)μmol/L和(210.97±136.59)μmol/L,两组差异有统计学意义(P=0.0115)。C4d阳性受者对激素和ATG冲击治疗与阴性受者比较,敏感率明显降低。C4d阳性的受者移植肾1年生存率较阴性受者低,分别为64.3%和90.0%,两组间差异有统计学意义(P=0.006)。结论移植肾C4d阳性的受者发生排斥反应时,对常规的激素冲击和ATG抗排斥治疗不敏感,血肌酐明显升高,移植肾1年存活率下降,受者预后较差。

Objective To explore the significance of peritubular capillary C4d deposition in the diagnosis, treatment and prognosis of the patients with acute renal allograft rejection. Methods 86 allograft biopsies obtained from 78 kidney transplants were examined by immunohistochemistry on routine paraffin sections using anti-CAd polyclonal antibody. The relationship of CAd and functions, therapies and prognoses of allografts was analyzed. Results There were 32 allograft biopsies with Banff type Ⅰ rejection, 51 with Banff type Ⅱ rejection and 3 with Banff type Ⅲ rejection. Thirty biopsies were positive in C4d deposition. For 28 patients, at least one biopsy exhibited peritubular CAd deposition. There was no significant difference between type Ⅰ and type Ⅱ rejection （21.9% vs 39. 2%, P= 0. 101）. The CAd^＋ group had proportionately more patients with pregnant history （P = 0. 020）, more patients with high panel-reactive antibody levels （P = 0. 013）, and more retransplanted patients （P = 0. 016）. Mean serum creatinine was significantly higher in CAd positive patients than in negative patients[（ 312. 56±196. 26） μmol/L vs （210.97± 136. 59）μmol/L, P = 0. 0115]. Patients with CAd deposition were more commonly resistant to antirejection therapy with bolus steroids （75.0 % vs 28. 0 %, P= 0. 000） and ATG （66. 7 % vs 12.5 %, P= 0. 027）. More patients with peritubular C4d deposition lost their grafts during the study period （64. 3 % vs 90.0 %, P = 0. 006）. Conclusion Acute rejection with C4d deposition were resistant to antirejection therapy with steroids and/or ATG, and associated with inferior graft outcome.