Maternal exposure to paternal HLA does not explain the postpartum increase in rheumatoid arthritis

The postpartum period, particularly after the first pregnancy, represents a time of increased risk for the development of rheumatoid arthritis (RA). The present study was undertaken to investigate whether this increase in risk may be due to maternal exposure to fetally inherited paternal HLA-DR antigens that were either 1) similar to their own or 2) had an increased likelihood of being one of the two specific types, HLA-DR1 and DR4, implicated in the etiology of RA. We recruited 94 families where the mother had developed RA within 12 months of a pregnancy, and HLA typed the mother, father, and relevant child of each family. Mothers were not more likely to share HLA-DR genes with their partners than would be expected, and children whose parents shared one HLA-DR gene were not more likely to inherit the shared gene from their father as opposed to the non-shared gene. Further, those children whose fathers were heterozygous for HLA-DR1 or DR4 were not more likely to inherit these genes as opposed to the non-DR1/DR4 gene. In conclusion, maternal exposure during pregnancy to either fetally inherited paternal HLA-DR1 and DR4 genes or to paternal DR genes similar to their own does not appear to contribute to postpartum maternal susceptibility of RA.