Maternal microchimerism in cord blood and childhood type 1 diabetes

Background: Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common and persists into adult life. MMc is thought to be involved in tissue regeneration and/or immunenological tolerance. MMc has been postilated to play a role in autoimmune diseases, and has been detected in the circulation and pancreas, with increase MMc frequency in type 1 diabetes (T1D) patients. This could be due to expansion of existing cells during disease development, but no studies have investigated whether those who later develop T1D have higher levels at birth. We investigated MMc in cord blood samples to test the hypothesis that MMc levels predict T1D risk. We also tested whether cord blood MMc correlated with MMc in plasma at T1D diagnosis.

Methods: Mothers and their offspring (n=1174 families) in the longitudinal MoBa birth cohort were HLA class II typed to determine non-inherited (and non-shared) maternal alleles (NIMA). MMc was estimated as maternal DNA quantitiy in the fetal circulation, by NIMA-specific digital droplet PCR. MMc was measured in cord blood pasma from 69 children who later developed T1D and 126 random controls (the NIMAs examined were HLA DQB1-0301, 0402 and 0602-0603 in 61, 27 and 107 children, respectively).

Results: We found detectable quantitites of MMc in 33/69 future T1D cases (48%) and 53/126 controls (42%), OR 1.3, 95%CI 0.7-2.3, with no significant difference in distributions between cases and controls (Mann-Whitney P=0.52). There was a non-significantly increased estimate in the NIMA DQB1-0301 subgroup (OR 2.4, 95%CI 0.8-7.3; Mann-Whitney test for difference between cases and controls P=0.07). The presence of measurable MMc in cord blood was not significantly associated with presence of MMC at diagnosis (OR=222, 95%CI 0.8-6.5, P=0.15). In conclusion, the hypothesis that higher levels of MMc in cord blood predicted lower T1D risk was not supported.