Yang L, Lu Y P, Luo G H, Song J, Tu Z D, Li Y P
Transplantation Institute, West China Hospital, Chengdu, Sichuan, China.
Transplant Proc. 2008 Oct;40(8):2786-9. doi: 10.1016/j.transproceed.2008.08.002.
Antivimentin antibody is often produced as an autoantibody after transplantation. C4d deposition, a marker of humoral immunity during transplantation, is believed to reflect alloantibodies. This study investigated the relationship between C4d deposition and humoral immunity to vimentin among rat kidneys undergoing chronic allograft nephropathy (CAN).
Fisher 344 rat renal grafts were orthotopically transplanted into Lewis rats following the procedure of Kamada with our modification. All recipients were administered cyclosporine (CsA) (10 mg/kg(-1).d(-1) x 10 d) before being divided into 3 groups of oral treatments: (1) vehicle, (2) CsA (6 mg/kg(-1).d(-1)), and (3) mycophenolate mofetil (MMF; 20 mg/kg(-1).d(-1)). At 4, 8 and 12 weeks after transplantation, the rats were killed, the renal allografts harvested, and the sera collected. Serum creatinine (SCr) was measured and pathologic changes assessed according to the Banff 97 criteria. The antivimentin antibody was quantified by enzyme-linked immunosorbent assay. The deposition of C4d detected by immunofluorescence was analyzed by integrated optical density (IOD).
Antivimentin antibody was observed in sera of all transplanted rats. The level of antivimentin antibody (IgGDeltaOD) increased gradually during the development of CAN from 4 weeks. Simultaneously, C4d deposition in peritubular capillaries also progressively strengthened. There was a strong positive correlation between the content of antivimentin antibody and C4d deposition (r = 0.892; P = .000). MMF simultaneously decreased antivimentin antibody formation and C4d deposition. In contrast, CsA had no significant effect.
We demonstrated the production of antivimentin antibodies and the deposition of C4d during the development of CAN. There was a positive correlation between them. Whether humoral immunity to vimentin contributes to C4d deposition is not clear and further studies are needed to elucidate this issue.
抗波形蛋白抗体在移植后常作为自身抗体产生。C4d沉积是移植过程中体液免疫的一个标志物，被认为可反映同种异体抗体。本研究调查了慢性移植肾肾病（CAN）大鼠肾脏中C4d沉积与针对波形蛋白的体液免疫之间的关系。
按照Kamada的方法并加以改进，将Fisher 344大鼠肾移植到Lewis大鼠体内。所有受体在接受环孢素（CsA）（10 mg/kg-1·d-1×10 d）治疗后，分为3组进行口服治疗：（1）赋形剂组，（2）CsA组（6 mg/kg-1·d-1），（3）霉酚酸酯（MMF；20 mg/kg-1·d-1）组。在移植后4、8和12周，处死大鼠，获取移植肾并收集血清。测量血清肌酐（SCr），并根据Banff 97标准评估病理变化。通过酶联免疫吸附测定法定量抗波形蛋白抗体。通过积分光密度（IOD）分析免疫荧光检测到的C4d沉积。
在所有移植大鼠的血清中均观察到抗波形蛋白抗体。从4周开始，在CAN发展过程中抗波形蛋白抗体水平（IgGΔOD）逐渐升高。同时，肾小管周围毛细血管中的C4d沉积也逐渐增强。抗波形蛋白抗体含量与C4d沉积之间存在强正相关（r = 0.892；P = 0.000）。MMF同时降低了抗波形蛋白抗体的形成和C4d沉积。相比之下，CsA没有显著影响。
我们证明了在CAN发展过程中抗波形蛋白抗体的产生和C4d的沉积。它们之间存在正相关。针对波形蛋白的体液免疫是否导致C4d沉积尚不清楚，需要进一步研究来阐明这一问题。
