NEONATAL LUPUS-ERYTHEMATOSUS - STUDIES ON HLA CLASS-II GENES AND AUTOANTIBODY PROFILES IN JAPANESE MOTHERS

Neonatal lupus erythematosus (NLE) is a rare disorder of neonates char acterized by two major clinical manifestations: congenital heart block and cutaneous lupus lesions. The disease is associated with placental ly transferred maternal anti-Ro/SSA and/or La/SSB antibodies. To clari fy possible class II HLA associations with maternal autoantibody respo nses, haplotypic and allelic distributions, along with the polymorphis m of the MHC class II HLA alleles, were analyzed based on PCR-RFLP res ults in 25 Japanese mothers of two groups defined by precipitating aut oantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SS B antibodies, but not those with anti-Ro/SSA alone, the class II haplo types DRB11101-DQA1*0501-DQB1*0301 and DRB1*08032-DQA1*0103-DQB1*0601 as well as individual class II alleles DRB11101, DRB1*08032 and DQB1 0301 showed significantly increased frequencies compared to those in normal controls. All anti-Ro/SSA and anti-La/SSB positive mothers carr ied DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the DRB1 chain. These mothers also carried homozygous or heterozygous DQ6 and DQ3 alleles that shared the same amino acid r esidues at positions 27-36 and 71-77 of hypervariable regions of the D QB1 chain. Furthermore, all mothers with both anti-Ro/SSA and anti-La/ SSB were homozygous for DPB10501. Nine of 10 anti-Ro/SSA and anti-La/ SSB-positive mothers, but only 6 of 15 mothers with anti-Ro/SSA alone, had affected infants. Thus, our findings suggest that there may be im munogenetic differences among mothers according to their autoantibody profiles, and that mothers with both anti-Ro/SSA and anti-La/SSB are m ore likely to have infants with NLE than mothers with anti-Ro/SSA alon e.