Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland.
Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland.
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DOI：
10.1016/j.kint.2017.04.028
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发表时间：
2017-11
影响因子：
19.6
通讯作者：
Kavanagh D
中科院分区：
文献类型：
--
作者：
Brocklebank V;Johnson S;Sheerin TP;Marks SD;Gilbert RD;Tyerman K;Kinoshita M;Awan A;Kaur A;Webb N;Hegde S;Finlay E;Fitzpatrick M;Walsh PR;Wong EKS;Booth C;Kerecuk L;Salama AD;Almond M;Inward C;Goodship TH;Sheerin NS;Marchbank KJ;Kavanagh D
因子H自身抗体可损害补体调节，导致非典型溶血性尿毒症综合征，主要发生在儿童时期。目前还没有研究治疗的试验，临床实践只有通过回顾队列分析才能获得信息。在这里，我们检查了英国和爱尔兰175名表现为非典型溶血性尿毒症综合征的儿童的H因子自身抗体，其中包括17名效价高于国际标准的儿童。在这17人中，有7人在编码补体途径成分或调节因子的基因中伴随着罕见的遗传变异。两名儿童接受了支持性治疗；两人都出现了明确的肾功能衰竭。在接受治疗的11名患者中，有7名患者的血浆置换与肾脏恢复率差有关。接受eculizumab治疗的6名患者恢复了肾功能。与全球惯例相反，出于对治疗相关并发症的担忧，没有采用免疫抑制疗法来防止血浆置换治疗患者的复发。在没有免疫抑制的情况下，复发率很高(7人中有5人)。然而，再次治疗导致了肾功能的恢复。所有接受eculizumab治疗的患者均获得持续缓解。5名患者接受了无特定因子H自身抗体靶向治疗的肾移植，其中1名患者也有显著的CFI基因突变，术后复发。因此，我们目前的做法是启动eculizumab治疗因子H自身抗体介导的非典型溶血性尿毒症综合征，而不是血浆置换加或不加免疫抑制。基于这一回顾分析，我们没有看到劣质治疗的迹象，尽管我们的结论的强度受到小样本数量的限制。
Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange–treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody–targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody–mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size.
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DOI：
10.1074/jbc.m114.630871
发表时间：
2015-04-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bhattacharjee A;Reuter S;Trojnár E;Kolodziejczyk R;Seeberger H;Hyvärinen S;Uzonyi B;Szilágyi Á;Prohászka Z;Goldman A;Józsi M;Jokiranta TS
通讯作者：
Jokiranta TS
影响因子：
4.6
作者：
Brocklebank V;Wong EK;Fielding R;Goodship TH;Kavanagh D
通讯作者：
Kavanagh D
影响因子：
5.7
作者：
Hofer, Johannes;Giner, Thomas;Jozsi, Mihaly
通讯作者：
Jozsi, Mihaly
确定CFHR3/CFHR1删除的总体频率在第1季度。
影响因子：
3.7
作者：
Holmes LV;Strain L;Staniforth SJ;Moore I;Marchbank K;Kavanagh D;Goodship JA;Cordell HJ;Goodship TH
通讯作者：
Goodship TH
影响因子：
13.6
作者：
Dragon-Durey, Marie-Agnes;Sethi, Sidharth Kumar;Fremeaux-Bacchi, Veronique
通讯作者：
Fremeaux-Bacchi, Veronique