Role of HLA in congenital heart block: susceptibility alleles in mothers

In congenital heart block (CHB), abnormal maternal immunisation leads to autoantibody production against SS-A/Ro and SS-B/La antigens. These maternal antibodies are transferred across the placenta to the unborn child and are believed to transmit irreversible immunological injury in developing foetal heart tissue, thus causing 3rd-degree atrioventricular block. The mothers may suffer from systemic lupus erythematosus (SLE) or primary Sj?gren's syndrome (SS), but they may be asymptomatic. Women with primary SS show a typical autoimmune HLA antigen pattern, namely higher frequency of HLA B8 and DR3 than in the normal population. The HLA pattern may affect individual ability to resist infecting bacteria and viruses and to response in various ways to autoantigens. It is probable that other factors such as genetic regulation of immune response are involved in CHB. We compared the HLA class I and class II alleles of mothers having CHB children with those of women suffering from primary SS and having healthy children, and with those of healthy Finns. Antibodies against 52-kD and 60-kD SS-A/Ro and 48-kD SS-B/La antigens were compared between the two groups of mothers. Our results show that anti-SS-A/Ro antibody-positive mothers all show a strong association with known autoimmune-predisposing HLA alleles, however, the mothers of CHB children differ in some HLA class I alleles, and especially in HLA haplotypes, from mothers of healthy children. Mothers with HLA A1, Cw7, B8 and without B15 are at particularly high-risk of having CHB children.