Neonatal lupus erythematosus: analysis of HLA class I genes in Japanese child/mother pairs

Abstract

Neonatal lupus erythematosus (NLE), characterized by two major symptoms of congenital heart block (CHB) and transient cutaneous lesions, is an antibody mediated disorder due to placentally transmitted maternal autoantibodies to Ro/SSA and/or La/SSB. We genotyped 14 mothers, 9 children with CHB, 8 with cutaneous NLE only and 5 asymptomatic siblings at HLA class I loci, by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with sequence-specific amplification. Mothers of children with NLE exhibited a very high polymorphism of HLA class I genes. Significant increases of HLA-B*1501 (B62) and Cw*0303 (Cw9) with absence of HLA-Al/B8 haplotype in Japanese mothers differed from the serologically defined HLA class I profiles among NLE mothers in white and North American black populations. Child/mother heterozygous HLA-A/B/C haplotype identity, which extended to HLA-class II DR/DQ loci, was observed in only one of 9 cases with CHB. No association was found between HLA class I alleles of children and the symptoms of NLE. These findings provide for the opportunity to investigate the primary genetic associations with NLE/CHB in different ethnic groups.

Keywords

neonatal lupus erythematosus congenital heart block HLA

Get full access to this article

View all access options for this article.

References

1 Silverman ED , Laxer RM . Neonatal lupus erythematosus . Rheum Dis Clin North Am 1997; 23: 599-618 .

2 Horsfall AC , Venables PJW , Taylor PV , Maini RN . Ro and La antigens and maternal anti-La idiotype on the surface of myocardial fibres in congential heart block . J Autoimmun 1991; 4: 165-176 .

3 Miyagawa S et al. Neonatal lupus erythematosus: haplotypic analysis of HLA class II alleles in child/mother pairs . Arthritis Rheum 1997; 40: 982-983 .

4 Siren MK et al. Role of HLA in congenital heart block: susceptibility alleles in children . Lupus 1999; 8: 60-67 .

5 Yoshida M , Kimura A , Numano F , Sasazuki T . Polymerase-chain-reaction-based analysis of polymorphism in the HLA-B gene . Hum Immunol 1992; 34: 257-266 .

6 Bunce M et al. Phototyping: comprehensive DNA typing for HLA-A,B,C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP) . Tissue Antigens 1995; 46: 355-367 .

7 Moribe T , Kaneshige T , Inoko H . Complete HLA-A DNA typing using the PCR-RFLP method combined with allele group-and sequence-specific amplification . Tissue Antigens 1997; 50: 535-545 .

8 Miyagawa S et al. Neonatal lupus erythematosus: HLA-DR and-DQ distributions are different among the groups of anti-Ro/SSA positive mothers with different neonatal outcomes . J Invest Dermatol 1997; 108: 881-885 .

9 Bodmer JG et al. Nomenclature for factors of the HLA system, 1996 . Hum Immunol 1997; 53: 98-128 .

10.

10 Marsh SGE . Nomenclature for factors of the HLA system, update April 1998 . Tissue Antigens 1998; 52: 300-300 .

11.

11 Hashimoto M et at. Gene frequencies and haplotypic associations within the HLA region in 916 unrelated Japanese individuals . Tissue Antigens 1994; 44: 166-173 .

12.

12 Yasunaga S et al. Different contribution of HLA-DR and-DQ genes in susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM) . Tissue Antigens 1996; 47: 37-48 .

13.

13 Watson RM et al. Neonatal lupus erythematosus syndrome: analysis of C4 allotypes and C4 genes in 18 families . Medicine 1992; 71: 84-95 .

14.

14 Lee LA et al. Immunogenetics of the neonatal lupus syndrome . Ann Intern Med 1983; 99: 592-596 .

15.

15 Brucato A et al. Isolated congenital heart block: longerm outcome of mothers, maternal antibody specificity and immunogenetic back-ground . J Rheumatol 1995; 22: 533-540 .

16.

16 Siren MK et al. Role of HLA in congenital heart block: susceptibility alleles in mothers . Lupus 1999; 8: 52-59 .