Background: Vertical transfer of maternal cells to the fetus via the placenta leads to maternal microchimerism (MMc) in children. Previous studies from USA have shown that the prevalence and degree of MMc was significantly higher in patients with type 1 diabetes (T1D) than in their unaffected siblings and control individuals. To date, however, the frequency of MMc in non-Caucasian T1D patients remains to be examined.
Methods: We studied 153 Japanese children diagnosed with T1D, including 122 children positive for diabetes-associated autoantibodies, and their 71 unaffected siblings. We examined the prevalence and degree of MMc in the DNA samples extracted from peripheral blood mononuclear cells by the use of quantitative PCR targeting non-transmitted maternal HLA alleles.
Results: MMc was detected in 18 of 122 children with autoantibody-positive T1D, 8 of 31 children with autoantibody-negative T1D, and 11 of 71 unaffected siblings. The prevalence of MMc was slightly higher in children with autoantibody-negative T1D than that of children with autoantibody-positive T1D and unaffected siblings; however, the difference was not statistically significant (P = 0.18 [autoantibody-negative T1D vs. autoantibody-positive T1D], P = 0.28 [autoantibody-negative T1D vs. unaffected siblings]). The median [minimum-max] MMc levels, calculated from the MMc cells per 100,000 proband cells, were comparable among these three groups (0.0 [0.0-15.4], 0.0 [0.0-12.6], and 0.0 [0.0-18.2], respectively).
Discussion: The prevalence and degree of MMc did not differ among children with T1D with and without autoantibodies and their unaffected siblings. These findings indicate that MMc plays a negligible role in the development of T1D in Japanese children. Notably, the median MMc levels of our patients with T1D were similar to those of the previously reported healthy Caucasian children. The difference in the MMc frequency between the present and previous studies may reflect the difference in the genetic background between Asian and Caucasian patients. Indeed, MMc has previously linked to the Caucasian-predominant risk HLA allele, DQB1*0302-DRB1*04. As yet, it remains unknown whether MMc is involved in autoimmune β-cell destruction or constitutes a protective response against tissue damage. Further studies are needed to confirm the role of MMc in childhood-onset T1D.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology