@article{8e6d2e89bbb44a8789a21dda326d2e89,
title = "Maternal microchimerism in cord blood and risk of childhood-onset type 1 diabetes",
abstract = "Background: Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common and persistent. MMc has been detected with increased frequency in the circulation and pancreas of type 1 diabetes (T1D) patients. We investigated for the first time whether MMc levels at birth predict future T1D risk. We also tested whether cord blood MMc predicted MMc in samples taken at T1D diagnosis. Methods: Participants in the Norwegian Mother and Child Cohort study were human leukocyte antigen (HLA) class II typed to determine non-inherited, non-shared maternal alleles (NIMA). Droplet digital (dd) polymerase chain reaction (PCR) assays specific for common HLA class II NIMA (HLADQB1*03:01, *04:02, and *06:02/03) were developed and validated. MMc was estimated as maternal DNA quantity in the fetal circulation, by NIMA specific ddPCR, measured in cord blood DNA from 71 children who later developed T1D and 126 controls within the cohort. Results: We found detectable quantities of MMc in 34/71 future T1D cases (48%) and 53/126 controls (42%) (adjusted odds ratio [aOR] 1.27, 95% confidence interval (CI) 0.68-2.36), and no significant difference in ranks of MMc quantities between cases and controls (Mann-Whitney P =.46). There was a possible association in the NIMA HLA-DQB1*03:01 subgroup with later T1D (aOR 3.89, 95%CI 1.05-14.4). MMc in cord blood was not significantly associated with MMc at T1D diagnosis. Conclusions: Our findings did not support the hypothesis that the degree of MMc in cord blood predict T1D risk. The potential subgroup association with T1D risk should be replicated in a larger cohort.",
keywords = "HLA, childhood, microchimerism, pregnancy, type 1 diabetes",
author = "German Tapia and Georgina Mortimer and Jody Ye and Gillard, {Benjamin T.} and Saranna Chipper-Keating and Karl M{\aa}rild and Viken, {Marte K.} and Lie, {Benedicte A.} and Geir Joner and Torild Skrivarhaug and Nj{\o}lstad, {P{\aa}l R.} and Ketil St{\o}rdal and Gillespie, {Kathleen M.} and Stene, {Lars C.}",
note = "Funding Information: The authors are grateful to Professor Klaus Badenhoop, Goethe University Frankfurt, Germany, for providing samples used to develop the ddPCR method. The Norwegian Mother and Child Cohort Study are supported by the Norwegian Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537-01 and grant no.2 UO1 NS 047537-06A1). We are grateful to all the participating families in Norway who take part in this on-going cohort study. The Norwegian Childhood Diabetes Registry is funded by The South-Eastern Norway Regional Health Authority. We are thankful to the Norwegian Childhood Diabetes Registry and to the Norwegian Childhood Diabetes Study Group. Dr. St{\o}rdal was supported by an unrestricted grant from the Oak Foundation, Geneva, Switzerland. Costs of all data acquisition, including laboratory assays in MoBa (the sub-study PAGE; Prediction of Autoimmune Diabetes and Celiac Disease in Childhood by Genes and Perinatal Environment), was supported by grant 2210909/F20 from the Norwegian Research Council (Dr. Stene). Dr. Nj{\o}lstad was supported by the European Research Council (AdG #293574), Stiftelsen Kristian Gerhard Jebsen, the Research Council of Norway (#240413), the Bergen Research Foundation, and the Western Health Authorities (Strategic Grant). Data from the Norwegian Patient Register has been used in this publication. The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by the Norwegian patient register is intended nor should be inferred. SNP genotyping in this study was performed at the Genomics Core Facility, Norwegian Radium hospital, Oslo, Norway. Funding Information: NIH/NIEHS, Grant/Award Number: N01-ES- 75558; NIH/NINDS, Grant/Award Numbers: UO1 NS 047537-01, UO1 NS 047537-06A1; Norges Forskningsr{\aa}d, Grant/Award Number: 2210909/F20; Research Foundation; the Research Council; Stiftelsen Kristian Gerhard Jebsen; European Research Council; Norwegian Research Council, Grant/Award Number: F20; Oak Foundation; Norwegian Ministry of Education and Research; Helse-og Omsorgsdepartementet Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",
year = "2019",
doi = "10.1111/pedi.12875",
language = "English (US)",
volume = "20",
pages = "728--735",
journal = "Pediatric Diabetes",
issn = "1399-543X",
publisher = "Blackwell Munksgaard",
number = "6",
}
