{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:30:08Z","timestamp":1786480208865,"version":"build-2736575974"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL 136348"],"award-info":[{"award-number":["R01HL 136348"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Women with severe preeclampsia demonstrate abnormal levels of the complement alternative pathway components.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Genetic variants in the complement alternative pathway are more prevalent in those with severe phenotype preeclampsia compared with the general population.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Future studies should explore the role of medications that block the complement alternative pathway in treatment of preeclampsia.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome share many clinical and biologic features with thrombotic microangiopathy syndromes caused by complement abnormalities. Our hypothesis was that similar functional and genetic alterations in the complement alternative pathway (CAP) are present in these disorders of pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted quantitative analysis of proteins involved in CAP using ELISA and nephelometry on prospectively collected blood samples from patients with severe phenotype preeclampsia (defined as delivery \u226434 weeks due to preeclampsia), HELLP syndrome, or eclampsia, and matched normotensive controls (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =25 in each arm) between 2011 and 2016. Sequencing was performed to interrogate 14 genes encoding CAP components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both groups were similar in age, gravidity, parity, marital status, and race. The study group had a higher BMI (mean\u00b1SD, 32\u00b18 versus 25\u00b14 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.002) and earlier gestational age at delivery (32.5\u00b13.6 versus 40.3\u00b11 weeks;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). Serologic studies demonstrated elevated Bb subunit (median [range], 1.2 [0.5\u20134.3] versus 0.6 [0.5\u20131]\n                      <jats:italic toggle=\"yes\">\u03bc<\/jats:italic>\n                      g\/ml; P&lt;0.001), complement C5 concentration (28 [18\u201333] versus 24 [15\u201334] mg\/dl;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.03), and sMAC (371 [167\u2013761] versus 184 [112\u2013249] ng\/ml; P&lt;0.001) concentrations in patients with preeclampsia. Two thirds of patients with preeclampsia had at least one nonsynonymous sequence variant in CAP genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with severe phenotype preeclampsia manifest functional alterations in CAP activation. Genetic variants in the CAP genes were detected in several patients, but a larger population study is necessary to fully evaluate genetic risk. Genetic screening and complement-targeted treatment may be useful in risk stratification and novel therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.34067\/kid.0000992021","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T16:05:10Z","timestamp":1625069110000},"page":"1463-1472","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Quantitative Alterations in Complement Alternative Pathway and Related Genetic Analysis in Severe Phenotype Preeclampsia"],"prefix":"10.34067","volume":"2","author":[{"given":"Layan","family":"Alrahmani","sequence":"first","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota"},{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Loyola University Medical Center, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Gonzalez Suarez","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot A.","family":"Cousin","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota"},{"name":"Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Moyer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alice V.","family":"Willrich","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy M.","family":"White","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myra J.","family":"Wick","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota"},{"name":"Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda J.","family":"Tostrud","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Narang","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department 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