TY - JOUR
T1 - Maternal Microchimerism in Cord Blood and Risk of Celiac Disease in Childhood
AU - Tapia, German
AU - Mortimer, Georgina
AU - Ye, Jody
AU - Mårild, Karl
AU - Chipper-Keating, Saranna
AU - Gillard, Benjamin T.
AU - Viken, Marte K.
AU - Lie, Benedicte A.
AU - Stene, Lars C.
AU - Gillespie, Kathleen M.
AU - Størdal, Ketil
N1 - Publisher Copyright:
Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Objectives:During pregnancy, small quantities of maternal cells are naturally transmitted to the fetus. This transmission, termed maternal microchimerism (MMc), has been implicated in autoimmune diseases but its potential role is unclear. We aimed to investigate if MMc at birth predicted childhood celiac disease (CD) risk, a common immune-mediated enteropathy often presenting in childhood.Methods:We designed a case-control study, nested in the Norwegian Mother, Father and Child Cohort. Participants were HLA class II typed to determine noninherited, nonshared maternal alleles (NIMA). Droplet digital (dd) PCR assays specific for common HLA class II NIMAs (HLA-DQB1∗03:01, ∗04:02 and ∗06:02/03) were used to estimate the quantity of maternal DNA, as a marker of maternal cells, in cord blood DNA from 124 children who later developed clinically diagnosed CD (median age at end of study 7.4 years, range 3.6-12.9) and 124 random controls. We tested whether presence of MMc was associated with CD using logistic regression, and compared ranks between cases and controls.Results:MMc, for example, maternal HLA antigens not inherited by the child, was found in 42% of cases and 43% of controls, and not associated with CD (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.58-1.60). The ranks of MMc quantities in cases and controls were also similar (Mann-Whitney U-test, P = 0.71). The subgroup with HLA-DQB1:03∗01 as their NIMA had a potential association with MMc, where levels greater than median was associated with CD (OR 3.78, 95% CI 1.28-11.18).Conclusion:MMc measured in cord blood was not associated with later risk of CD.
AB - Objectives:During pregnancy, small quantities of maternal cells are naturally transmitted to the fetus. This transmission, termed maternal microchimerism (MMc), has been implicated in autoimmune diseases but its potential role is unclear. We aimed to investigate if MMc at birth predicted childhood celiac disease (CD) risk, a common immune-mediated enteropathy often presenting in childhood.Methods:We designed a case-control study, nested in the Norwegian Mother, Father and Child Cohort. Participants were HLA class II typed to determine noninherited, nonshared maternal alleles (NIMA). Droplet digital (dd) PCR assays specific for common HLA class II NIMAs (HLA-DQB1∗03:01, ∗04:02 and ∗06:02/03) were used to estimate the quantity of maternal DNA, as a marker of maternal cells, in cord blood DNA from 124 children who later developed clinically diagnosed CD (median age at end of study 7.4 years, range 3.6-12.9) and 124 random controls. We tested whether presence of MMc was associated with CD using logistic regression, and compared ranks between cases and controls.Results:MMc, for example, maternal HLA antigens not inherited by the child, was found in 42% of cases and 43% of controls, and not associated with CD (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.58-1.60). The ranks of MMc quantities in cases and controls were also similar (Mann-Whitney U-test, P = 0.71). The subgroup with HLA-DQB1:03∗01 as their NIMA had a potential association with MMc, where levels greater than median was associated with CD (OR 3.78, 95% CI 1.28-11.18).Conclusion:MMc measured in cord blood was not associated with later risk of CD.
KW - celiac disease
KW - childhood
KW - human leucocyte antigen
KW - microchimerism
KW - mother and child cohort study
KW - pregnancy
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UR - http://www.scopus.com/inward/citedby.url?scp=85090074932&partnerID=8YFLogxK
U2 - 10.1097/MPG.0000000000002811
DO - 10.1097/MPG.0000000000002811
M3 - Article
C2 - 32833392
AN - SCOPUS:85090074932
SN - 0277-2116
VL - 71
SP - 321
EP - 327
JO - Journal of pediatric gastroenterology and nutrition
JF - Journal of pediatric gastroenterology and nutrition
IS - 3
ER -