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

In congenital heart block (CHB), abnormal maternal immunisation leads to au toantibody 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 Sjogren's syn drome (SS), but they may be asymptomatic. Women with primary SS show a typi cal autoimmune HLA antigen pattern, namely higher frequency of HLA B8 and D R3 than in the normal population. The HLA pattern may affect individual abi lity to resist infecting bacteria and viruses and to response in various wa ys to autoantigens. It is probable that other factors such as genetic regul ation of immune response are involved in CHB. We compared the HLA class I a nd class II alleles of mothers having CHB children with those of women suff ering from primary SS and having healthy children, and with those of health y Finns. Antibodies against 52-kD and 60-kD SS-A/Ro and 48-kD SS-B/La antig ens 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 k nown autoimmune-predisposing HLA alleles, however. the mothers of CHB child ren differ in some HLA class I alleles, and especially in HLA haplotypes, f rom mothers of healthy children. Mothers with HLA Al, Cw7, Bs and without B 15 are at particularly high risk of having CHB children.