The Fertility Clinic 4071, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Am J Reprod Immunol. 2011 Jul;66 Suppl 1:93-100. doi: 10.1111/j.1600-0897.2011.01038.x.
Cellular and humoral immune responses against male-specific minor histocompatibility (HY) antigens are important in the pathogenesis of graft-versus-host reactions and can be detected in women who have previously given birth to a boy. However, the importance of these responses for pregnancy outcome is unclear.
Review of the current knowledge about the impact of anti-HY immunity on pregnancy outcome in terms of risk of miscarriage, placental abruption and low birth weight.
Women with secondary recurrent miscarriage (RM) more often have given birth to a boy compared with a girl prior to a series of miscarriages (P<0.0001) and a firstborn boy seems significantly to reduce the chance of a subsequent live in these patients (P=0.0003). Human leukocyte antigen (HLA) class II alleles known to restrict CD4 T-cell-mediated anti-HY responses were investigated among 358 patients with secondary RM and 203 of their children born prior to the miscarriages. The chance of a subsequent live birth in secondary RM patients with firstborn boys compared with firstborn girls was significantly lower in women with HY-restricting HLA class II alleles [OR: 0.17 (0.1-0.4), P=0.0001]. In patients without these alleles, the chance of live birth was similar in those with firstborn boys and girls, respectively. In early pregnancy, both antibodies against HLA and HY antigens were found with increased prevalence in secondary patients with RM and in particular in those with a firstborn boy compared with controls (P=0.005). The presence of these antibodies was associated with a low subsequent live birth rate, and the presence of HY antibodies was associated with a low male/female ratio (12% boys versus 88% girls) in subsequent live births (P=0.03). Register-based population studies suggested that births of boys also are associated with subsequent adverse obstetric outcomes also in the background population.
Findings strongly indicate that aberrant maternal immune reactions against fetal HY antigens playing a role in secondary RM and other pregnancy complications. We propose pathogenetic pathways for these conditions that in our view best explain the findings.
针对男性特异性次要组织相容性（HY）抗原的细胞和体液免疫反应在移植物抗宿主反应的发病机制中很重要，并且可以在以前生过男孩的女性中检测到。然而，这些反应对妊娠结局的重要性尚不清楚。
综述了目前关于抗 HY 免疫对妊娠结局的影响的知识，包括流产、胎盘早剥和低出生体重的风险。
与一系列流产前相比，有继发性复发性流产（RM）的女性更常生男孩（P<0.0001），而且第一胎男孩明显降低了这些患者后续活产的机会（P=0.0003）。在 358 例继发性 RM 患者和 203 例流产前出生的患儿中，调查了已知限制 CD4 T 细胞介导的抗 HY 反应的人类白细胞抗原（HLA）II 类等位基因。与第一胎女孩相比，第一胎男孩的继发性 RM 患者后续活产的机会在具有 HY 限制 HLA II 类等位基因的女性中明显较低[比值比：0.17（0.1-0.4），P=0.0001]。在没有这些等位基因的患者中，第一胎男孩和女孩的活产机会相似。在早期妊娠中，与对照组相比，继发性 RM 患者，尤其是第一胎男孩，抗 HLA 和 HY 抗原的抗体均以更高的患病率存在（P=0.005）。这些抗体的存在与随后的活产率低相关，而 HY 抗体的存在与随后的活产儿中男性/女性比例低（12%男孩对 88%女孩）相关（P=0.03）。基于登记的人群研究表明，男孩的出生也与背景人群中的后续不良产科结局相关。
研究结果强烈表明，针对胎儿 HY 抗原的母体免疫反应异常在继发性 RM 和其他妊娠并发症中起作用。我们提出了这些疾病的发病机制途径，我们认为这些途径最能解释这些发现。
