Neonatal lupus erythematosus: HLA-DR and -DQ distributions are different among the groups of anti-Ro/SSA-positive mothers with different neonatal outcomes.
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.
Miyagawa
S
S
Department of Dermatology, Nara Medical University, Kashihara City, Japan.
Shinohara
K
K
Kidoguchi
K
K
Fujita
T
T
Fukumoto
T
T
Yamashina
Y
Y
Hashimoto
K
K
Yoshioka
A
A
Sakurai
S
S
Nishihara
O
O
Shirai
T
T
D000328:Adult; D000483:Alleles; D000596:Amino Acids / Q000032:analysis; D000974:Antibodies, Antinuclear / Q000032:analysis* / Q000097:blood; D015551:Autoimmunity; D015984:Causality; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000032:analysis* / Q000235:genetics; D006684:HLA-DR Antigens / Q000032:analysis* / Q000235:genetics; D006239:Haplotypes; D006327:Heart Block / Q000151:congenital / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008178:Lupus Erythematosus, Cutaneous / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D008431:Maternal-Fetal Exchange; D008875:Middle Aged; D011247:Pregnancy / Q000276:immunology*; D011256:Pregnancy Outcome; D012867:Skin / Q000737:chemistry / Q000473:pathology
D000596:Amino Acids; D000974:Antibodies, Antinuclear; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; C035356:SS-A antibodies; C035357:SS-B antibodies