Miyagawa S, Shinohara K, Kidoguchi K, Fujita T, Fukumoto T, Hashimoto K, Yoshioka A, Shirai T
Department of Dermatology, Nara Medical University, Kashihara City, Japan.
Autoimmunity. 1997;26(2):95-101. doi: 10.3109/08916939709003852.
Neonatal lupus erythematosus (NLE) is a rare disorder of neonates characterized by two major clinical manifestations: congenital heart block and cutaneous lupus lesions. The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. To clarify possible class II HLA associations with maternal autoantibody responses, haplotypic and allelic distributions, along with the polymorphism of the MHC class II HLA alleles, were analyzed based on PCR-RFLP results in 25 Japanese mothers of two groups defined by precipitating autoantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SSB antibodies, but not those with anti-Ro/SSA alone, the class II haplotypes DRB11101-DQA10501-DQB10301 and DRB108032-DQA10103-DQB10601 as well as individual class II alleles DRB11101, DRB108032 and DQB10301 showed significantly increased frequencies compared to those in normal controls. All anti-Ro/SSA and anti-La/SSB positive mothers carried 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 residues at positions 27-36 and 71-77 of hypervariable regions of the DQB1 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 immunogenetic differences among mothers according to their autoantibody profiles, and that mothers with both anti-Ro/SSA and anti-La/SSB are more likely to have infants with NLE than mothers with anti-Ro/SSA alone.
新生儿红斑狼疮（NLE）是一种罕见的新生儿疾病，其主要临床表现有两种：先天性心脏传导阻滞和皮肤狼疮损害。该疾病与经胎盘转移的母体抗Ro/SSA和/或La/SSB抗体有关。为了阐明可能的II类HLA与母体自身抗体反应、单倍型和等位基因分布的关联，以及MHC II类HLA等位基因的多态性，基于PCR-RFLP结果，对两组由沉淀性自身抗体谱定义的25名日本母亲的MHC II类HLA等位基因进行了分析。在同时具有抗Ro/SSA和抗La/SSB抗体的母亲中，而非仅具有抗Ro/SSA抗体的母亲中，II类单倍型DRB11101-DQA10501-DQB10301和DRB108032-DQA10103-DQB10601以及单个II类等位基因DRB11101、DRB108032和DQB10301的频率与正常对照组相比显著增加。所有抗Ro/SSA和抗La/SSB阳性的母亲都携带在DRB1链的第14 - 31位和第71位具有相同氨基酸残基的DRB1等位基因。这些母亲还携带在DQB1链高变区的第27 - 36位和第71 - 77位具有相同氨基酸残基的纯合或杂合DQ6和DQ3等位基因。此外，所有同时具有抗Ro/SSA和抗La/SSB的母亲均为DPB10501纯合子。10名抗Ro/SSA和抗La/SSB阳性的母亲中有9名婴儿患病，但15名单独具有抗Ro/SSA抗体的母亲中只有6名婴儿患病。因此，我们的研究结果表明，根据自身抗体谱，母亲之间可能存在免疫遗传学差异，并且同时具有抗Ro/SSA和抗La/SSB的母亲比仅具有抗Ro/SSA的母亲更有可能生出患NLE的婴儿。
