© 1995 British Society for Rheumatology
research-article |
MATERNAL HLA ANTIGENS AND ANTIBODIES TO SS-A/RO AND SS-B/LA. COMPARISON WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND PRIMARY SJÖGREN’S SYNDROME
Fourth Department of Medicine, Helsinki University Central Hospital Unioninkatu 38, 00170 Helsinki
*Finnish Red Cross Blood Transfusion Centre Kivihaantie 7, 00310 Helsinki
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital Haartmanninkatu 2, 00290 Helsinki
Department of Bacteriology and Immunology, Helsinki University Haartmanninkatu 3, 00290 Helsinki, Finland
Correspondence to:
Correspondence to: H.Julkunen, Peijas Hospital, Sairaalakatu I, 04100, Vanatas, Finland.
To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers of affected children were HLA typed for class I and II antigens, and the results were compared with the corresponding HLA types in 900 healthy controls, in 45 mothers with systemic lupus erythematosus (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 often than healthy controls [71 vs 20%; relative risk (RR) 9.8, P <0.00001 and 74 vs 23% RR 9.8, P <0.0001, respectively]. HLA B35 was protective (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 controls 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 more closely related to primary SS than to SLE. Levels of antibodies to all three SS-A/Ro antigens were significantly higher in mothers of children 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 similar (P = 0.32-0.66). HLA B8, DR3, DQ2 and heterozygosity for DQ1/DQ2 were strongly associated with all three assays for antibodies to SS-A/Ro (P =0.0001–0.018). The corresponding associations with antibodies to SS7-B/La were weaker (P = 0.0076–1.0). The common immunogenetic background of the mother for having a child with CHB is the presence of HLA antigens B8, DR3 and DQ2 associated with high levels of antibodies to SS7-A/Ro. Mothers of children with CHB are genetically more closely related to patients with primary SS than to patients with SLE.
KEY WORDS: Congenital heart block, HLA antigens, SS-A/Ro antibodies, SS-B/La antibodies, Systemic lupus erythematosus, Primary Sjögren's syndrome