J Pediatr Gastroenterol Nutr. 2020 Sep;71(3):321-327. doi: 10.1097/MPG.0000000000002811.

German Tapia ¹, Georgina Mortimer ², Jody Ye ², Karl Mårild ³, Saranna Chipper-Keating ², Benjamin T Gillard ², Marte K Viken ⁴, Benedicte A Lie ^4 5, Lars C Stene ¹, Kathleen M Gillespie ², Ketil Størdal ^1 6

Author information

• ¹Norwegian Institute of Public Health, Oslo, Norway.
• ²Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, UK.
• ³Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg and Queen Silvia Children's Hospital, Gothenburg, Sweden.
• ⁴Department of Immunology, Rikshospitalet, Oslo University Hospital.
• ⁵Department of Medical Genetics, University of Oslo, Oslo.
• ⁶Pediatric Department, Østfold Hospital Trust, Grålum, Norway.

Abstract

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-DQB103:01, 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.