TY - JOUR
T1 - Direct evidence of complement activation in HELLP syndrome
T2 - A link to atypical hemolytic uremic syndrome
AU - Vaught, Arthur J.
AU - Gavriilaki, Eleni
AU - Hueppchen, Nancy
AU - Blakemore, Karin
AU - Yuan, Xuan
AU - Seifert, Sara M.
AU - York, Sarah
AU - Brodsky, Robert A.
N1 - Funding Information:
EG was supported by the Johns Hopkins University School of Medicine Visiting Scientist LIBRA Initiative as a Johns Hopkins Libra Fellow during the performance of this study. AV has received funding from the Johns Hopkins University School of Medicine Synergy Award for Innovative Research. Dr. Sammy Zakaria has supported this project as a co-investigator.
Publisher Copyright:
© 2016 ISEH - International Society for Experimental Hematology.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.exphem.2016.01.005
DO - 10.1016/j.exphem.2016.01.005
M3 - Article
C2 - 26921648
AN - SCOPUS:84963600144
SN - 0301-472X
VL - 44
SP - 390
EP - 398
JO - Experimental Hematology
JF - Experimental Hematology
IS - 5
ER -