University of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, France.
Department of Pathology, Gui de Chauliac Hospital, Montpellier University Hospital, Montpellier, France.
Front Immunol. 2019 Mar 8;10:235. doi: 10.3389/fimmu.2019.00235. eCollection 2019.
C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9-indicative of complement-mediated injury-is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25-73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival ( = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9- ABMR (median time after transplantation, 28 vs. 85 months; = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients.
C4d 在肾小管毛细血管（PTC）中的沉积反映了肾移植抗体介导排斥反应（ABMR）中的补体激活。然而，其与移植物存活的关系存在争议。我们假设 C5b9 指示的补体介导损伤的毛细血管沉积是 ABMR 的严重程度标志物。本研究旨在确定这些沉积在 ABMR 中的频率、位置和预后影响。我们回顾性地选择了 2005 年 1 月至 2014 年 12 月在法国两个移植中心诊断为 ABMR 的患者，并通过免疫组织化学法进行 C4d 和 C5b9 染色。共纳入 54 例患者。中位随访时间为 52.5（34.25-73.5）个月。13 例（24%）患者肾小球毛细血管（GC）有 C5b9 沉积。其中 7 例（54%）呈弥漫性分布。12 例 C5b9+患者的 GC 和 PTC 也有 C4d 沉积。GC 和 PTC 上的 C4d 沉积与受死亡限制的移植物存活率无关（分别为 0.42 和 0.69）。然而，GC 中 C5b9 弥漫性沉积的患者与节段性或无沉积的患者相比，受死亡限制的移植物存活率明显较低（ABMR 诊断后中位生存时间，分别为 6 个月、40.5 个月和 44 个月； = 0.015）。与 C5b9-ABMR 相比，C5b9+ABMR 患者的肾小球基底膜双轮廓更早出现在移植后（中位时间，28 与 85 个月； = 0.058）。总之，我们发现了一种新的 C5b9+ABMR 模式，与肾小球基底膜复制的早期发生和移植物存活率差有关。补体抑制剂可能是这类患者的一种治疗选择。
