Human leukocyte antigens and fetal microchimerism: Relating fetal-origin cells in maternal circulation to maternal and fetal HLA genetics

Fetal microchimerism denotes the presence of small amounts of fetal cells within the mother, which may persist for decades after pregnancy. The mechanisms by which these semiallogeneic cells avoid alloreactivity and manage to persist for years within the host are unknown. Previous reports have linked microchimerism to human leukocyte antigen (HLA) variants, such as HLA-C groups based on killer cell Immunoglobulin-like receptor (KIR) reactivity, HLA-DQA1*05:01, and soluble HLA-G (sHLA-G). In the present study, we attempt to verify these associations during pregnancy and postpartum. We included 255 pregnant women and 188 women between one and eight years postpartum. Data on HLA-C and HLADQA genotypes, as well as maternal circulating sHLA-G were available for a varying number of women, with cohorts ranging from 167 to 252 during pregnancy and 79-118 postpartum. Maternal and fetal HLA-C groups did not correlate with microchimerism during pregnancy or postpartum. HLA-C group mismatch from the perspective of the mother, on the other hand, negatively correlated with presence and quantity of fetal microchimerism in maternal circulation in the postpartum cohort, but not during pregnancy. Neither HLA-DQA1*05:01 nor circulating levels of sHLA-G were associated with microchimerism measurements. We confirm a negative correlation between circulating fetal microchimerism postpartum and fetal-maternal HLA-C mismatch based on KIR reactivity. Considering that such an association was not found at an HLA-C allele level in a previous publication, our present observation indicates that the interaction between microchimeric cell HLA-C variants and host killer-cell immunoglobulin-like receptors may be relevant for the longevity of microchimerism.