Maternal cells have recently been found in the circulation and tissues of mothers' immune-competent children, including in adult life, and is referred to as maternal microchimerism (MMc). Whether MMc confers benefits during development or later in life or sometimes has adverse effects is unknown. Type 1 diabetes (T1D) is an autoimmune disease that primarily affects children and young adults. To identify and quantify MMc, we developed a panel of quantitative PCR assays targeting nontransmitted, nonshared maternal-specific HLA alleles. MMc was assayed in peripheral blood from 172 individuals, 94 with T1D, 54 unaffected siblings, and 24 unrelated healthy subjects. MMc levels, expressed as the genome equivalent per 100,000 proband cells, were significantly higher in T1D patients than unaffected siblings and healthy subjects. Medians and ranges, respectively, were 0.09 (0 -530), 0 (0 -153), and 0 (0 -7.9). Differences between groups were evident irrespective of HLA genotypes. However, for patients with the T1D-associated DQB1*0302-DRB1*04 haplotype, MMc was found more often when the haplotype was paternally (70%) rather than maternally transmitted (14%). In other studies, we looked for female islet ␤ cells in four male pancreases from autopsies, one from a T1D patient, employing FISH for X and Y chromosomes with concomitant CD45 and ␤ cell insulin staining. Female islet ␤ cells (presumed maternal) formed 0.39 -0.96% of the total, whereas female hematopoietic cells were very rare. Thus, T1D patients have higher levels of MMc in their circulation than unaffected siblings and healthy individuals, and MMc contributes to islet ␤ cells in a mother's progeny.quantitative PCR ͉ chimerism ͉ autoimmunity ͉ pancreas ͉ HLA

Fetal cells derived from pregnancy can persist in a woman's blood and tissues for decades and have been implicated in the pathogenesis of autoimmune disease. Transplantation studies based on donor sex mismatch suggest that circulating stem cells can lead to liver regeneration with donor-derived hepatocytes. However, male cells in female liver could derive from pregnancy. We investigated male cells in liver biopsies from women with sons and asked whether they were hematopoietic cells or hepatocytes. Fluorescence in situ hybridization for X-and Y-chromosomes with concomitant immunohistochemistry was employed to study 28 female liver biopsies: 14 with the autoimmune disease primary biliary cirrhosis (PBC), eight with Hepatitis C, and six with other diseases. Total male cells and those expressing hematopoietic (CD45) or hepatocyte (CAM-5.2) markers were quantified. None of the male cells were hematopoietic in origin, as shown by lack of CD45 expression. Instead, male cells with hepatocyte morphology expressing the hepatocyte marker CAM 5.2 were found in 25% of all biopsies (36% of PBC and 14% of others). Overall, male cells were found in 36% of female liver biopsies. Of the PBC livers 43% had male cells compared to 25% of Hepatitis C biopsies and 33% of others. There was a trend toward increased numbers of male cells in PBC compared to others (mean 1 per 30 000 host cells vs 0.17 in Hepatitis C and 0.35 in others). Thus, male cells found in livers of women with sons include cells that express hepatocyte antigens. Therefore, transplantation and stem cell differentiation studies using sex difference to conclude that donor cells regenerate liver may be confounded by fetal microchimerism. Whether fetal cells play a role in autoimmune diseases like PBC merits further investigation.

An increase of DRB1*11 in SSc is consistent with other reports. Although present in both diffuse and limited SSc disease subsets, the increase was predominantly due to over-representation of DRB1*1104 in women with diffuse SSc. Women with limited SSc had a preponderance of DRB1*1101, the most common allele in healthy women. DRB1*1104 and DRB1*1101 differ by a single amino acid at position 86, where the former has valine and the latter glycine.