TY - JOUR
T1 - Urinary excretion of C5b-9 in severe preeclampsia tipping the balance of complement activation in pregnancy
AU - Burwick, Richard M.
AU - Fichorova, Raina N.
AU - Dawood, Hassan Y.
AU - Yamamoto, Hidemi S.
AU - Feinberg, Bruce B.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - The complement cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. Consequently, biomarkers of complement dysregulation may be useful for prediction or treatment of disease. Because renal damage with proteinuria is a characteristic pathological feature of preeclampsia, we hypothesized that complement markers in urine, rather than plasma, could better reflect complement dysregulation in disease. To investigate this, we performed a case-control study of pregnant women, enrolling 25 cases with severe preeclampsia, 25 controls with chronic hypertension, and 25 healthy controls without hypertension matched by gestational age and parity. Subjects were recruited from the Brigham and Women's Hospital from March 2012 to March 2013. Urine and blood samples were collected on the day of enrollment, with complement activation (C3a, C5a, and C5b-9) measured by ELISA. Severe preeclampsia was associated with marked elevations in urinary C5b-9 (median [interquartile range], 4.3 [1.2-15.1] ng/mL) relative to subjects with chronic hypertension (0 [0-0]) and healthy controls (0 [0-0]; P<0.0001). Urinary excretion of C5b-9 was detected in 96% of cases with severe preeclampsia, 12% of controls with chronic hypertension, and 8% of healthy controls. Cases were also notable for significantly greater urinary excretion of C3a and C5a. Plasma levels of C5a and C5b-9, but not C3a, were increased in the cases with severe preeclampsia compared with healthy controls; however, they did not distinguish preeclampsia from chronic hypertension, supporting our hypothesis that complement markers in urine, rather than plasma, better reflect complement dysregulation. Complement inhibition is an intriguing treatment option for patients with severe preeclampsia.
AB - The complement cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. Consequently, biomarkers of complement dysregulation may be useful for prediction or treatment of disease. Because renal damage with proteinuria is a characteristic pathological feature of preeclampsia, we hypothesized that complement markers in urine, rather than plasma, could better reflect complement dysregulation in disease. To investigate this, we performed a case-control study of pregnant women, enrolling 25 cases with severe preeclampsia, 25 controls with chronic hypertension, and 25 healthy controls without hypertension matched by gestational age and parity. Subjects were recruited from the Brigham and Women's Hospital from March 2012 to March 2013. Urine and blood samples were collected on the day of enrollment, with complement activation (C3a, C5a, and C5b-9) measured by ELISA. Severe preeclampsia was associated with marked elevations in urinary C5b-9 (median [interquartile range], 4.3 [1.2-15.1] ng/mL) relative to subjects with chronic hypertension (0 [0-0]) and healthy controls (0 [0-0]; P<0.0001). Urinary excretion of C5b-9 was detected in 96% of cases with severe preeclampsia, 12% of controls with chronic hypertension, and 8% of healthy controls. Cases were also notable for significantly greater urinary excretion of C3a and C5a. Plasma levels of C5a and C5b-9, but not C3a, were increased in the cases with severe preeclampsia compared with healthy controls; however, they did not distinguish preeclampsia from chronic hypertension, supporting our hypothesis that complement markers in urine, rather than plasma, better reflect complement dysregulation. Complement inhibition is an intriguing treatment option for patients with severe preeclampsia.
KW - Complement system proteins
KW - Eculizumab
KW - Hellp syndrome
KW - Preeclampsia
KW - Pregnancy
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U2 - 10.1161/HYPERTENSIONAHA.113.01420
DO - 10.1161/HYPERTENSIONAHA.113.01420
M3 - Article
C2 - 24060886
AN - SCOPUS:84891594043
VL - 62
SP - 1040
EP - 1045
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 6
ER -