The association between circulating SIGLEC6 and preeclampsia: observational studies of seven cohortsResearch in context

Summary: Background: Preeclampsia is a serious complication of pregnancy. Methods: We did an observational study using seven tissue bank/cohorts to examine the association between circulating SIGLEC6 and preeclampsia. We included samples from participants with preterm disease (delivering <34 wee...

Full description

Saved in:
Bibliographic Details
Main Authors: Tu'uhevaha J. Kaitu'u-Lino, Teresa M. MacDonald, Emerson Keenan, Roxanne Hastie, Catherine A. Cluver, Daniella Susic, Amanda Henry, Jenny E. Myers, Lesley M. McCowan, Rennae S. Taylor, Lina Bergman, Francine Z. Marques, David M. Kaye, Lucy A. Bartho, Natalie J. Hannan, Ping Cannon, Tuong-Vi Nguyen, Manju Kandel, Ciara Murphy, Georgia P. Wong, Joshua Masci, Natasha Pritchard, Susan P. Walker, Stephen Tong
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396425003147
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849239337534750720
author Tu'uhevaha J. Kaitu'u-Lino
Teresa M. MacDonald
Emerson Keenan
Roxanne Hastie
Catherine A. Cluver
Daniella Susic
Amanda Henry
Jenny E. Myers
Lesley M. McCowan
Rennae S. Taylor
Lina Bergman
Francine Z. Marques
David M. Kaye
Lucy A. Bartho
Natalie J. Hannan
Ping Cannon
Tuong-Vi Nguyen
Manju Kandel
Ciara Murphy
Georgia P. Wong
Joshua Masci
Natasha Pritchard
Susan P. Walker
Stephen Tong
author_facet Tu'uhevaha J. Kaitu'u-Lino
Teresa M. MacDonald
Emerson Keenan
Roxanne Hastie
Catherine A. Cluver
Daniella Susic
Amanda Henry
Jenny E. Myers
Lesley M. McCowan
Rennae S. Taylor
Lina Bergman
Francine Z. Marques
David M. Kaye
Lucy A. Bartho
Natalie J. Hannan
Ping Cannon
Tuong-Vi Nguyen
Manju Kandel
Ciara Murphy
Georgia P. Wong
Joshua Masci
Natasha Pritchard
Susan P. Walker
Stephen Tong
author_sort Tu'uhevaha J. Kaitu'u-Lino
collection DOAJ
description Summary: Background: Preeclampsia is a serious complication of pregnancy. Methods: We did an observational study using seven tissue bank/cohorts to examine the association between circulating SIGLEC6 and preeclampsia. We included samples from participants with preterm disease (delivering <34 weeks gestation in Australia), examined whether levels altered with clinical disease severity (samples collected in South Africa) and whether there were alterations preceding disease onset using samples collected at 15- and 20-weeks' gestation in New Zealand, samples collected between 26 and 34 weeks in the UK and samples collected at 28 or 36 weeks gestation in Australia. Circulating SIGLEC6, sFlt-1, and PlGF were measured via ELISA or a electrochemiluminescence immunoassay platform. Findings: SIGLEC6 was elevated 9.5-fold (23,397 pg/ml, IQR 16701–32,267) in preterm preeclampsia (<34 weeks gestation), compared to normotensive pregnancies (2441 pg/ml, IQR 871.9–6547; p = 6.3 × 10−9). SIGLEC6 levels correlated with disease severity: compared to preeclampsia without severe features, SIGLEC6 was raised 1.5–2.5-fold with eclampsia, or preeclampsia with life-threatening complications. There was a stepwise increase in SIGLEC6 with increasing numbers of maternal complications, accentuated when expressed as a SIGLEC6/PlGF ratio (10.7-fold rise with ≥3 maternal complications, versus no complications). Circulating SIGLEC6 concentrations were significantly increased among those later diagnosed with preeclampsia in samples collected at 36 weeks (n = 1032; Australia), 26–34 weeks (n = 235; UK), 28 (n = 283; Australia), and 20 weeks' gestation (n = 1945; New Zealand). Interpretation: SIGLEC6 is elevated with preeclampsia and levels correlate with disease severity. Funding: National Health and Medical Research Council (#1065854) and the Norman Beischer Medical Research Foundation. Additional sources of funding for the biobank from South Africa was received from the Swedish Medical Society, Märta Lundqvist Foundation, Swedish Foundation for International Cooperation in Research and Higher Education, Jane and Dan Olssons Foundation, Mercy Perinatal (Australia), the Swedish Research Council (Vetenskaps-rådet), Sweden, and the Center for Clinical Research Dalarna, Sweden. The MAViS study (UK) was funded through National Institute Health Research (NIHR-CS-011-020). MUMS was funded by a St George and Sutherland Medical Research Foundation of Australia grant.Salary or scholarship support was received from: Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) Taylor Hammond Scholarship to TM; National Health and Medical Research Council Fellowships to ST (#2017897) and DMK (#2008017); Australian Research Council Future Fellowships to TKL (FT230100125) and NJH (FT210100193), Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation Fellowship and a National Heart Foundation Future Leader Fellowship (#105663) to FZM.
format Article
id doaj-art-dff6630a4073402cbef243e26bd03654
institution Kabale University
issn 2352-3964
language English
publishDate 2025-08-01
publisher Elsevier
record_format Article
series EBioMedicine
spelling doaj-art-dff6630a4073402cbef243e26bd036542025-08-20T04:01:02ZengElsevierEBioMedicine2352-39642025-08-0111810587010.1016/j.ebiom.2025.105870The association between circulating SIGLEC6 and preeclampsia: observational studies of seven cohortsResearch in contextTu'uhevaha J. Kaitu'u-Lino0Teresa M. MacDonald1Emerson Keenan2Roxanne Hastie3Catherine A. Cluver4Daniella Susic5Amanda Henry6Jenny E. Myers7Lesley M. McCowan8Rennae S. Taylor9Lina Bergman10Francine Z. Marques11David M. Kaye12Lucy A. Bartho13Natalie J. Hannan14Ping Cannon15Tuong-Vi Nguyen16Manju Kandel17Ciara Murphy18Georgia P. Wong19Joshua Masci20Natasha Pritchard21Susan P. Walker22Stephen Tong23Translational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia; Corresponding author. Translational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaThe Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Women's and Children's Health, Uppsala University, Uppsala, SwedenTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; Department of Obstetrics and Gynecology, Tygerberg Hospital, Stellenbosch University, Cape Town, South AfricaDiscipline of Women's Health, School of Clinical Medicine, UNSW Medicine and Health, University of New South Wales, Sydney, Australia; Department of Women's and Children's Health, St George Hospital, Sydney, AustraliaDiscipline of Women's Health, School of Clinical Medicine, UNSW Medicine and Health, University of New South Wales, Sydney, Australia; Department of Women's and Children's Health, St George Hospital, Sydney, AustraliaUniversity of Manchester, Manchester Academic Health Science Centre, Manchester, United KingdomDepartment of Obstetrics and Gynaecology, University of Auckland, Auckland, New ZealandDepartment of Obstetrics and Gynaecology, University of Auckland, Auckland, New ZealandDepartment of Obstetrics and Gynecology, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Women's and Children's Health, Uppsala University, Uppsala, SwedenHypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, Australia; Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, AustraliaHeart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Cardiology, Alfred Hospital, Melbourne, Australia; Central Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, AustraliaThe Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaThe Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaTranslational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia; The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, AustraliaSummary: Background: Preeclampsia is a serious complication of pregnancy. Methods: We did an observational study using seven tissue bank/cohorts to examine the association between circulating SIGLEC6 and preeclampsia. We included samples from participants with preterm disease (delivering <34 weeks gestation in Australia), examined whether levels altered with clinical disease severity (samples collected in South Africa) and whether there were alterations preceding disease onset using samples collected at 15- and 20-weeks' gestation in New Zealand, samples collected between 26 and 34 weeks in the UK and samples collected at 28 or 36 weeks gestation in Australia. Circulating SIGLEC6, sFlt-1, and PlGF were measured via ELISA or a electrochemiluminescence immunoassay platform. Findings: SIGLEC6 was elevated 9.5-fold (23,397 pg/ml, IQR 16701–32,267) in preterm preeclampsia (<34 weeks gestation), compared to normotensive pregnancies (2441 pg/ml, IQR 871.9–6547; p = 6.3 × 10−9). SIGLEC6 levels correlated with disease severity: compared to preeclampsia without severe features, SIGLEC6 was raised 1.5–2.5-fold with eclampsia, or preeclampsia with life-threatening complications. There was a stepwise increase in SIGLEC6 with increasing numbers of maternal complications, accentuated when expressed as a SIGLEC6/PlGF ratio (10.7-fold rise with ≥3 maternal complications, versus no complications). Circulating SIGLEC6 concentrations were significantly increased among those later diagnosed with preeclampsia in samples collected at 36 weeks (n = 1032; Australia), 26–34 weeks (n = 235; UK), 28 (n = 283; Australia), and 20 weeks' gestation (n = 1945; New Zealand). Interpretation: SIGLEC6 is elevated with preeclampsia and levels correlate with disease severity. Funding: National Health and Medical Research Council (#1065854) and the Norman Beischer Medical Research Foundation. Additional sources of funding for the biobank from South Africa was received from the Swedish Medical Society, Märta Lundqvist Foundation, Swedish Foundation for International Cooperation in Research and Higher Education, Jane and Dan Olssons Foundation, Mercy Perinatal (Australia), the Swedish Research Council (Vetenskaps-rådet), Sweden, and the Center for Clinical Research Dalarna, Sweden. The MAViS study (UK) was funded through National Institute Health Research (NIHR-CS-011-020). MUMS was funded by a St George and Sutherland Medical Research Foundation of Australia grant.Salary or scholarship support was received from: Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) Taylor Hammond Scholarship to TM; National Health and Medical Research Council Fellowships to ST (#2017897) and DMK (#2008017); Australian Research Council Future Fellowships to TKL (FT230100125) and NJH (FT210100193), Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation Fellowship and a National Heart Foundation Future Leader Fellowship (#105663) to FZM.http://www.sciencedirect.com/science/article/pii/S2352396425003147PreeclampsiaBiomarkerPregnancySIGLEC6Placenta
spellingShingle Tu'uhevaha J. Kaitu'u-Lino
Teresa M. MacDonald
Emerson Keenan
Roxanne Hastie
Catherine A. Cluver
Daniella Susic
Amanda Henry
Jenny E. Myers
Lesley M. McCowan
Rennae S. Taylor
Lina Bergman
Francine Z. Marques
David M. Kaye
Lucy A. Bartho
Natalie J. Hannan
Ping Cannon
Tuong-Vi Nguyen
Manju Kandel
Ciara Murphy
Georgia P. Wong
Joshua Masci
Natasha Pritchard
Susan P. Walker
Stephen Tong
The association between circulating SIGLEC6 and preeclampsia: observational studies of seven cohortsResearch in context
EBioMedicine
Preeclampsia
Biomarker
Pregnancy
SIGLEC6
Placenta
title The association between circulating SIGLEC6 and preeclampsia: observational studies of seven cohortsResearch in context
title_full The association between circulating SIGLEC6 and preeclampsia: observational studies of seven cohortsResearch in context
title_fullStr The association between circulating SIGLEC6 and preeclampsia: observational studies of seven cohortsResearch in context
title_full_unstemmed The association between circulating SIGLEC6 and preeclampsia: observational studies of seven cohortsResearch in context
title_short The association between circulating SIGLEC6 and preeclampsia: observational studies of seven cohortsResearch in context
title_sort association between circulating siglec6 and preeclampsia observational studies of seven cohortsresearch in context
topic Preeclampsia
Biomarker
Pregnancy
SIGLEC6
Placenta
url http://www.sciencedirect.com/science/article/pii/S2352396425003147
work_keys_str_mv AT tuuhevahajkaituulino theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT teresammacdonald theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT emersonkeenan theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT roxannehastie theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT catherineacluver theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT daniellasusic theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT amandahenry theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT jennyemyers theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT lesleymmccowan theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT rennaestaylor theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT linabergman theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT francinezmarques theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT davidmkaye theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT lucyabartho theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT nataliejhannan theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT pingcannon theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT tuongvinguyen theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT manjukandel theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT ciaramurphy theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT georgiapwong theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT joshuamasci theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT natashapritchard theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT susanpwalker theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT stephentong theassociationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT tuuhevahajkaituulino associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT teresammacdonald associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT emersonkeenan associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT roxannehastie associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT catherineacluver associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT daniellasusic associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT amandahenry associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT jennyemyers associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT lesleymmccowan associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT rennaestaylor associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT linabergman associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT francinezmarques associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT davidmkaye associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT lucyabartho associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT nataliejhannan associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT pingcannon associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT tuongvinguyen associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT manjukandel associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT ciaramurphy associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT georgiapwong associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT joshuamasci associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT natashapritchard associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT susanpwalker associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext
AT stephentong associationbetweencirculatingsiglec6andpreeclampsiaobservationalstudiesofsevencohortsresearchincontext