Abstract
Congenital complete heart block (CCHB) occurs in the offspring of mothers who have the HLA-A1;B8; DR3 haplotype and Ro (SS-A) autoantibodies. It has been shown that the presence of HLA-DR3 in mothers may facilitate Ro synthesis, but may not, by itself, be sufficient to induce CCHB in the offspring. However, maternal DR3 and Ro antibody seem to be independent factors associated with CCHB. Other HLA antigens, including class III (complement) genes, may also be necessary to induce CCHB in newborns since A1;B8; DR3 haplotypes, together with BfS and/or C4AQ0B1, are increased in Ro+ mothers of infants with CCHB compared with both controls and with Ro+ mothers whose offspring do not have CCHB. On the other hand, DR3 genes in a different HLA haplotype (i.e., B18; BfF1;DR3) are nonpathogenetic; this latter finding may be due to a DR3 gene's intrinsic difference or to the influence of neighboring genes. Also, a trend toward DR3 bias transmission is observed in DR3+ mothers who are also Ro+; fetal DR3 might protect the fetus against in utero death when Ro antibodies are present.
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