Neonatal Lupus Erythematosus: HLA-DR and -DQ Distributions Are Different among the Groups of Anti-Ro/SSA-Positive Mothers with Different Neonatal Outcomes

Abstract

Neonatal lupus erythematosus (NLE) is an antibody-mediated disorder of infants characterized by two major clinical manifestations; cutaneous lupus lesions and congenital heart block (CHB). The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. There is a tendency for the same disease expression to occur within a sibship. To reveal a possible association of class II MHC genes with maternal anti-Ro/SSA autoimmune responses and neonatal outcomes in NLE with a relatively homogeneous ethnic background, haplotype, and allele distributions were analyzed based on the PCR-RFLP results in 26 Japanese anti-Ro/SSA-positive mothers from three groups defined by neonatal outcomes. The results were as follows: (i) maternal HLA-DR5 haplotype DRB1*1101-DQA1*0501-DQB1*0301 and individual class II alleles making up this haplotype were significantly associated with neonatal cutaneous lupus but not CHB. Conversely, maternal HLA-DQB1*0602 carried on HLA-DR2 haplotypes was associated with CHB but not cutaneous NLE; (ii) HLA-DQA1 alleles with glutamine at position 34 of the first domain, which have reportedly been associated with the autoimmune responses to Ro/SSA antigens in other ethnic groups, were increased in the mothers of infants with cutaneous involvement; and (iii) there was no particular class II HLA profile that distinguished the disease manifestations in infants. These findings suggest that specific maternal MHC class II genes might correlate with specific neonatal outcomes in NLE.

DNA typing of maternal HLA in congenital complete heart block: Comparison with systemic lupus erythematosus and primary Sj�gren's syndrome

“…Among Japanese mothers of children with NLE, there were higher frequencies of DRB1*1101, DRB1*08032, and DQB1*0301 than in normal controls (31), but the maternal haplotype DRB1*1101;DQA1*0501;DQB1*0301 and the individual alleles making up this haplotype were associated with neonatal cutaneous lupus, not CCHB (32). In our sample, we detected an increased prevalence of the DRB1*11;DQA1*0501;DQB1*0301 haplotype and alleles in CCHB mothers compared with SLE, but not SS, control mothers.…”

Sjögren’s Syndrome: Autoantibodies to Cellular Antigens

“…In fact, a recent study in Japanese women reveals that the maternal HLA-DR5 haplotype DRB1*1101-DQA1*0501-DQB1*0301 was significantly associated with neonatal cutaneous lupus but not congenital heart block in contrast to maternal HLA-DQB1*0602 carried on HLA-DR2 haplotypes which was correlated with congenital heart block but not cutaneous neonatal lupus [74].…”

The clinical spectrum of autoimmune congenital heart block

“…Data from our systematic review. 14–19,21–24,27–29,31–33,36,38,40–43,45–51,100,101 Abbreviations: AD, autoimmune disease; aSS, Sjögren syndrome associated with other systemic autoimmune diseases; CHB, congenital heart block; pSS, primary Sjögren syndrome; RA, rheumatoid arthritis; SSc, systemic sclerosis; SLE, systemic lupus erythematosus; UAD, undifferentiated autoimmune disease.…”

“…15,17,21,22,24,25,28,32,40,43,48,49,51,68,69,102–104 Graphs depict a | age at diagnosis of CHB ( n =280), 15,17,22,24,25,28,32,33,40,42,48,62,68,69 b | CHB type ( n =772), 2,17,21,23–26,29,33,35,37,44,46,49,51,102 c | other cardiac complications ( n =875), 17,22,24,25,29,30,32,33,40,48,49,51,69,73,102,103 and d | mortality ( n =188). 15,17,21,22,24,25,28,30,32,33,38,40,43,48,49,51,68,69,102,103 Abbreviations: CHB, congenital heart block; EFE, endocardial fibroelastosis; IUGR, intrauterine growth restriction.…”