title: Overactivation of Complement Alternative Pathway in Postpartum Atypical Hemolytic Uremic Syndrome Patients with Renal Involvement.
abstract: OBJECTIVE
  Postpartum atypical hemolytic uremic syndrome (aHUS) is a life-threatening syndrome with unclear pathogenesis. The current study aimed to investigate the clinical and pathological features, complement activation status, and the genetic variations in a Chinese cohort of patients with renal biopsy-proven postpartum aHUS.
  
  
  METHODS
  Five patients with postpartum aHUS were recruited. Renal biopsy specimens were examined and scored. Plasma levels of complements were detected, and coding sequences of complement regulators were screened. Anti-CFH/CFI autoantibodies were further detected.
  
  
  RESULTS
  Patients with postpartum aHUS patients presented with severe clinical manifestations and renal involvement. The renal biopsies of the five patients showed typical features of thrombotic microangiopathies. The levels of the following complement components, C4d, Bb, C3a, C5a, and SC5b-9, were significantly elevated in patients with postpartum aHUS compared with normal non-pregnant controls. The plasma levels of CFH and CFI significantly decreased in patients with postpartum aHUS compared with normal pregnant women. Three CFH single nucleotide polymorphisms (SNPs) were identified in the five patients. Two patients presented with CFH autoantibodies.
  
  
  CONCLUSIONS
  Postpartum aHUS is a clinical syndrome with severe renal damage. Genetic deficiencies and autoantibodies of CFH may lead to alternative pathway overactivation and participated in the pathogenesis of postpartum aHUS.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Peking University Institute of Nephrology, Beijing, China.|Key laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Song
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Peking University Institute of Nephrology, Beijing, China.|Key laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Peking University Institute of Nephrology, Beijing, China.|Key laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China.
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors.forename: Bing-Ning
authors.initials: BN
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors.forename: Ying-Dong
authors.initials: YD
authors.lastname: He
authors.affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Peking University Institute of Nephrology, Beijing, China.|Key laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China.
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Wang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Peking University Institute of Nephrology, Beijing, China.|Key laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.affiliation: Institute for Translational Medicine and Therapeutics and Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Song
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Peking University Institute of Nephrology, Beijing, China.|Key laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
mesh_terms: D000328:Adult; D065766:Atypical Hemolytic Uremic Syndrome / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001706:Biopsy; D003167:Complement Activation; D017242:Complement Factor H / Q000235:genetics / Q000276:immunology*; D017244:Complement Factor I / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000276:immunology*; D005260:Female; D006801:Humans; D007155:Immunologic Factors; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008775:Methylprednisolone / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049590:Postpartum Period / Q000276:immunology*; D011247:Pregnancy
chemical_list: D001323:Autoantibodies; D007155:Immunologic Factors; D017242:Complement Factor H; C493611:CFI protein, human; D017244:Complement Factor I; D008775:Methylprednisolone
keywords: Complement alternative pathway; complement factor H; postpartum atypical hemolytic uremic syndrome; thrombotic microangiopathies