title: Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.
abstract: HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.
authors.affiliation: Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Vaught
authors.affiliation: Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Eleni
authors.initials: E
authors.lastname: Gavriilaki
authors.affiliation: Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hueppchen
authors.affiliation: Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Karin
authors.initials: K
authors.lastname: Blakemore
authors.affiliation: Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Seifert
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Sarah
authors.initials: S
authors.lastname: York
authors.affiliation: Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: rbrodsky@jhmi.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D065766:Atypical Hemolytic Uremic Syndrome / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D016022:Case-Control Studies; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000187:drug effects / Q000502:physiology*; D005260:Female; D017359:HELLP Syndrome / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D011247:Pregnancy; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015938:Complement Membrane Attack Complex; C481642:eculizumab