Maternal microchimerism in cord blood and risk of childhood‐onset type 1 diabetes

• Published in: Pediatric diabetes 2019-09, Vol.20 (6), p.728-735, Article pedi.12875
• Main Authors: Tapia, German, Mortimer, Georgina, Ye, Jody, Gillard, Benjamin T., Chipper‐Keating, Saranna, Mårild, Karl, Viken, Marte K., Lie, Benedicte A., Joner, Geir, Skrivarhaug, Torild, Njølstad, Pål R., Størdal, Ketil, Gillespie, Kathleen M., Stene, Lars C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age of Onset; Case-Control Studies; Child; Childhood; Children; Chimerism; Cohort Studies; Cord blood; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diagnosis; DNA; Female; Fetal Blood - cytology; Fetal Blood - immunology; Fetal Blood - metabolism; Fetuses; Follow-Up Studies; Gene Frequency; Genetic Predisposition to Disease; Histocompatibility antigen HLA; HLA; HLA Antigens - genetics; Humans; Infant, Newborn; Male; microchimerism; Mothers; Pancreas; Polymerase chain reaction; Pregnancy; Risk Factors; type 1 diabetes; Young Adult
• ISSN: 1399-543X; 1399-5448
• DOI: 10.1111/pedi.12875

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.