Kumar Ashwani, Ramachandran Raja, Rawat Amit, Das Reena, Rayat Charan S, Kenwar Deepesh B, Sharma Ashish, Gupta Krishan L, Nada Ritambhra
Department of Histopathology, PGIMER, Chandigarh, India.
Department of Nephrology, PGIMER, Chandigarh, India.
Clin Kidney J. 2019 Nov 4;14(1):291-300. doi: 10.1093/ckj/sfz135. eCollection 2021 Jan.
Complement 3 glomerulopathy (C3G) results from dysfunction of the alternative complement pathway (ACP). No data are available on post-transplant C3G in South Asia.
In this study, renal allograft biopsies of C3G patients performed from 2012 to 2017 were analysed for ACP functional assay (APFA), serum complement levels, complement factor H (CFH), complement factor B (CFB) and autoantibodies to CFH and CFB. Limited genetic screening for / genes was carried out. All study patients were also followed up.
A total of 21 cases of C3G were included, of which 11 had native C3G disease (that is, recurrent C3G). Of these 11 recurrent cases, 7 presented with allograft dysfunction and 4 with proteinuria and renal dysfunction. Early post-transplant recurrence (<1 month) was noted in six patients, whereas recurrence in five patients occurred within 8-17 months of transplant. Biopsies showed mild focal mesangial expansion with or without endocapillary proliferation and thrombotic microangiopathy. Rejection was also noted in six patients. APFA/C3 levels were low in all cases. Serum CFH levels were low [dense deposit disease (DDD), 44%; C3 glomerulonephritis (C3GN), 25%], whereas CFB levels were normal. Autoantibodies to CFH, CFB and C3 nephritic factor were present in 11, 0 and 44% of DDD cases, respectively, and in 17, 17 and 33% of C3GN cases, respectively. Genetic analysis revealed only non-pathogenic gene variants (93%). No novel mutation was found. At follow-up (140 months), stable graft was noted in 28% of cases, progressive renal failure in 19%, graft loss in 34%, and 19% of patients died.
Post-transplant C3G can present with graft dysfunction and/or proteinuria. Subtle histological findings demand careful interpretation of immunofluorescence results. Autoantibodies to complement pathway regulatory proteins are common, and no novel mutation has been found from limited genetic workup. Clinical outcome is poor.
补体3肾小球病（C3G）是由替代补体途径（ACP）功能障碍引起的。南亚地区关于移植后C3G的数据尚不可得。
在本研究中，对2012年至2017年期间进行的C3G患者肾移植活检组织进行了ACP功能检测（APFA）、血清补体水平、补体因子H（CFH）、补体因子B（CFB）以及针对CFH和CFB的自身抗体分析。对相关基因进行了有限的基因筛查。所有研究患者也进行了随访。
共纳入21例C3G患者，其中11例有原发性C3G疾病（即复发性C3G）。在这11例复发病例中，7例出现移植肾功能障碍，4例出现蛋白尿和肾功能障碍。6例患者在移植后早期复发（<1个月），而5例患者在移植后8 - 17个月复发。活检显示轻度局灶性系膜扩张，伴或不伴毛细血管内增生和血栓性微血管病。6例患者也出现了排斥反应。所有病例的APFA/C3水平均较低。血清CFH水平较低[致密物沉积病（DDD），44%；C3肾小球肾炎（C3GN），25%]，而CFB水平正常。DDD病例中分别有11%、0%和44%存在针对CFH、CFB和C3肾炎因子的自身抗体，C3GN病例中分别有17%、17%和33%存在。基因分析仅发现非致病性基因变异（93%）。未发现新的突变。随访（140个月）时，28%的病例移植肾稳定，19%出现进行性肾衰竭，34%移植肾丢失，19%的患者死亡。
移植后C3G可表现为移植肾功能障碍和/或蛋白尿。细微的组织学表现需要仔细解读免疫荧光结果。针对补体途径调节蛋白的自身抗体很常见，有限的基因检查未发现新的突变。临床结局较差。
