MATERNAL HLA ANTIGENS AND ANTIBODIES TO SS-A RO AND SS-B/LA - COMPARISON WITH SYSTEMIC LUPUS-ERYTHEMATOSUS AND PRIMARY SJOGRENS-SYNDROME/

To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers of affected children were HLA typed for class I and II anti gens, and the results were compared with the corresponding HLA types i n 900 healthy controls, in 45 mothers with systemic lupus erythematosu s (SLE) and in 21 mothers with primary SS who had healthy children. An enzyme-linked immunosorbent assay was used to study the autoantibody responses to the recombinant 52 and 60 kDa SS-A/Ro, and 48 kDa SS-B/La proteins, and to the affinity-purified SS-A/Ro and SS-B/La antigens. Mothers of children with CHB had HLA B8 and DR3 significantly more oft en than healthy controls [71 vs 20%; relative risk (RR) 9.8, P < 0.000 01 and 74 vs 23%; RR 9.8, P < 0.0001, respectively]. HLA B35 was prote ctive (RR 0.1, P = 0.0029). Compared to controls with SLE, mothers of children with CHB were more often HLA DR3 and DQ2 positive (RR 4.1, P = 0.0057 and RR 3.1, P = 0.031, respectively), and compared to control s with primary SS less often HLA B15 positive (RR 0.1, P = 0.010). In general, the HLA antigen profile in mothers of children with CHB was m ore closely related to primary SS than to SLE. Levels of antibodies to all three SS-A/Ro antigens were significantly higher in mothers of ch ildren with CHB than in controls with SLE and primary SS (P = 0.0001-0 .0014). With regard to SS-B/La, the autoantibody responses were simila r (P = 0.32-0.66). HLA B8, DR3, DQ2 and heterozygosity for DQ1/DQ2 wer e strongly associated with all three assays for antibodies to SS-A/Ro (P = 0.0001-0.018). The corresponding associations with antibodies to SS-B/La were weaker (P = 0.0076-1.0). The common immunogenetic backgro und of the mother for having a child with CHB is the presence of HLA a ntigens B8, DR3 and DQ2 associated with high levels of antibodies to S S-A/Ro. Mothers of children with CHB are genetically more closely rela ted to patients with primary SS than to patients with SLE.