German Tapia1, Georgina Mortimer2, Jody Ye2, Benjamin T Gillard2, Saranna Chipper-Keating2, Karl Mårild1, Marte K Viken3, Benedicte A Lie3,4, Geir Joner5,6, Torild Skrivarhaug5,6, Pål R Njølstad7,8, Ketil Størdal1,9, Kathleen M Gillespie2, Lars C Stene1. 1. Norwegian Institute of Public Health, Oslo, Norway. 2. Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, UK. 3. Department of Immunology, Rikshospitalet, Oslo University Hospital, Oslo, Norway. 4. Department of Medical Genetics, University of Oslo, Oslo, Norway. 5. Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. 6. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 7. Department of Pediatric and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway. 8. KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. 9. Pediatric Department, Østfold Hospital Trust, Grålum, Norway.
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.
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.
Authors: Raj Shree; Stephen McCartney; Emma Cousin; Angel Chae; Hilary S Gammill; J L Nelson; Sami B Kanaan Journal: Reprod Sci Date: 2022-09-27 Impact factor: 2.924