title: Why are levels of maternal microchimerism higher in type 1 diabetes pancreas?
abstract: Maternal microchimerism (MMc) results from transfer of maternal cells to the fetus in pregnancy. These cells have been shown to persist into adulthood in healthy individuals and an increased frequency of MMc has been associated with autoimmune disease. Female (presumed maternal) islet beta cells have recently been identified at higher levels in pancreas from a child with T1D compared to three controls. There was, however, no evidence that these cells were the targets of autoimmune attack. The aim of this study was to analyze well-characterized T1D pancreases encompassing a spectrum in age at diagnosis, and duration of diabetes, for the presence of maternal microchimerism compared to control pancreases.Pancreas samples were available from six males with T1D and four male controls. Fluorescent-labeled probes were used to detect X and Y chromosomes. At least 1,000 cells, usually 4,000-8,000 cells underwent confocal imaging for each pancreas. The frequency of MMc was higher in T1D pancreases (range 0.31-0.80%, mean 0.58%) than in controls (0.24-0.50%, mean 0.38%) (p = 0.05). Intriguingly, clusters of 2-3 MMc were occasionally found in the pancreases, particularly T1D pancreases, suggesting replication of these cells. Concomitant FISH and immunofluorescence staining for insulin or CD45 was performed to phenotype cells of maternal origin. Insulin positive and insulin negative MMc were identified indicating that MMc contribute to the exocrine and endocrine compartments. No CD45 positive MMc were observed. These data confirm the presence of maternal cells in human pancreas and support previous observations that levels of MMc are higher in T1D pancreas compared to controls. MMc do not appear to be immune effector cells and those that stain positive for insulin within intact islets in T1D tissue appear healthy with no evidence that they are the focus of immune attack. This study adds support to the hypothesis that maternal stem cells have the capacity to cross the placental barrier and differentiate into both endocrine and exocrine cells but more detailed characterization of MMc in the pancreas is required.
authors.affiliation: Diabetes and Metabolism; Department of Clinical Science at North Bristol; University of Bristol; Bristol, UK.
authors.forename: Berendine
authors.initials: B
authors.lastname: Vanzyl
authors.forename: Raquel
authors.initials: R
authors.lastname: Planas
authors.forename: Yi
authors.initials: Y
authors.lastname: Ye
authors.forename: Alan
authors.initials: A
authors.lastname: Foulis
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: Marta
authors.initials: M
authors.lastname: Vives-Pi
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gillespie