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...
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2025-08-01
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| 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 |
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| 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 |
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