PMID- 31173445 OWN - NLM STAT- MEDLINE DCOM- 20200515 LR - 20200515 IS - 1399-5448 (Electronic) IS - 1399-543X (Linking) VI - 20 IP - 6 DP - 2019 Sep TI - Maternal microchimerism in cord blood and risk of childhood-onset type 1 diabetes. PG - 728-735 LID - 10.1111/pedi.12875 [doi] AB - 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. CI - (c) 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Tapia, German AU - Tapia G AUID- ORCID: 0000-0002-1770-1183 AD - Norwegian Institute of Public Health, Oslo, Norway. FAU - Mortimer, Georgina AU - Mortimer G AD - Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, UK. FAU - Ye, Jody AU - Ye J AD - Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, UK. FAU - Gillard, Benjamin T AU - Gillard BT AD - Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, UK. FAU - Chipper-Keating, Saranna AU - Chipper-Keating S AD - Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, UK. FAU - Marild, Karl AU - Marild K AD - Norwegian Institute of Public Health, Oslo, Norway. FAU - Viken, Marte K AU - Viken MK AD - Department of Immunology, Rikshospitalet, Oslo University Hospital, Oslo, Norway. FAU - Lie, Benedicte A AU - Lie BA AD - Department of Immunology, Rikshospitalet, Oslo University Hospital, Oslo, Norway. AD - Department of Medical Genetics, University of Oslo, Oslo, Norway. FAU - Joner, Geir AU - Joner G AD - Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Skrivarhaug, Torild AU - Skrivarhaug T AD - Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Njolstad, Pal R AU - Njolstad PR AD - Department of Pediatric and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway. AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. FAU - Stordal, Ketil AU - Stordal K AD - Norwegian Institute of Public Health, Oslo, Norway. AD - Pediatric Department, Ostfold Hospital Trust, Gralum, Norway. FAU - Gillespie, Kathleen M AU - Gillespie KM AD - Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, UK. FAU - Stene, Lars C AU - Stene LC AD - Norwegian Institute of Public Health, Oslo, Norway. LA - eng GR - N01-ES-75558/ES/NIEHS NIH HHS/United States GR - UO1 NS 047537-01/NS/NINDS NIH HHS/United States GR - UO1 NS 047537-06A1/NS/NINDS NIH HHS/United States GR - ERC_/European Research Council/International PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190619 PL - Denmark TA - Pediatr Diabetes JT - Pediatric diabetes JID - 100939345 RN - 0 (HLA Antigens) SB - IM MH - Adolescent MH - Adult MH - Age of Onset MH - Case-Control Studies MH - Child MH - *Chimerism MH - Cohort Studies MH - Diabetes Mellitus, Type 1/epidemiology/*genetics/immunology MH - Female MH - Fetal Blood/*cytology/immunology/*metabolism MH - Follow-Up Studies MH - Gene Frequency MH - Genetic Predisposition to Disease MH - HLA Antigens/genetics MH - Humans MH - Infant, Newborn MH - Male MH - Mothers MH - Risk Factors MH - Young Adult OTO - NOTNLM OT - HLA OT - childhood OT - microchimerism OT - pregnancy OT - type 1 diabetes EDAT- 2019/06/08 06:00 MHDA- 2020/05/16 06:00 CRDT- 2019/06/08 06:00 PHST- 2018/11/21 00:00 [received] PHST- 2019/04/05 00:00 [revised] PHST- 2019/05/28 00:00 [accepted] PHST- 2019/06/08 06:00 [pubmed] PHST- 2020/05/16 06:00 [medline] PHST- 2019/06/08 06:00 [entrez] AID - 10.1111/pedi.12875 [doi] PST - ppublish SO - Pediatr Diabetes. 2019 Sep;20(6):728-735. doi: 10.1111/pedi.12875. Epub 2019 Jun 19.