Department of Clinical Immunology, Instituto de Medicina de Laboratorio (IML) and Fundación para la Investigación Biomédica del Hospital Clínico San Carlos (IDISCC), Hospital Universitario Clínico San Carlos, Madrid, Spain.
Department of Immunology, Ophthalmology and Otorhinolaryngology (ENT), School of Medicine, Universidad Complutense, Madrid, Spain.
Front Immunol. 2024 Oct 24;15:1451552. doi: 10.3389/fimmu.2024.1451552. eCollection 2024.
The prevalence of gluten-related disorders, mainly celiac disease (CD) and non-celiac gluten sensitivity (NCGS), varies between 0.6% and 13% in the general population. There is controversial evidence regarding the association of both CD and NCGS with extra-digestive manifestations, including recurrent reproductive failure (RRF), which may have clinical implications.
To study the prevalence of HLA susceptibility alleles for CD/NCGS in a cohort of female patients with RRF from a single reference center and to evaluate the effect of a gluten-free diet on reproductive success.
A retrospective study was conducted on 173 patients with RRF, consecutively attended at the Reproductive Immunology Unit of San Carlos University Clinical Hospital in Madrid. We collected and analyzed the clinical, analytical, and immunological profiles of RRF patients who presented HLA alleles associated with CD and NCGS (HLA DQ2.2, DQ2.5, DQ8, and DQ7.5).
We observed a significantly higher prevalence of HLA alleles associated with CD and NCGS in our RRF cohort compared to the prevalence in the general population (69% vs. 35%-40%, p<0.0001). Only 2.3% of patients met the criteria for a CD diagnosis. In our RRF cohort, HLA-genetic susceptibility for CD/NCGS (HLA-risk group) was associated with a significantly higher rate of hypothyroidism compared to patients without these alleles (HLA-negative group) (48.7% vs. 26.92%, p=0.03). Patients with HLA-genetic susceptibility for CD/NCGS and thyroid disease had a significantly higher success rate in the subsequent pregnancy after management (55% vs. 30%, p=0.002). Two factors were found to be significant in this group: a gluten-free diet (p=0.019) and the use of levothyroxine (p=0.042).
In our cohort of RRF patients, we observed a significantly higher prevalence of HLA susceptibility genes for CD/NCGS compared to the general population, also associated with a higher incidence of thyroid alterations. A gluten-free diet and the use of levothyroxine in cases of thyroid pathology had significant beneficial effects on pregnancy outcomes. We suggest that HLA typing for CD/NCGS and a gluten-free diet, in the presence of risk alleles, can improve pregnancy outcomes in RRF patients.
在普通人群中，与麸质相关的疾病（主要为乳糜泻（CD）和非乳糜泻麸质敏感（NCGS））的患病率在 0.6%至 13%之间。关于 CD 和 NCGS 与消化系统外表现（包括复发性生殖失败（RRF））的关联，存在有争议的证据，这可能具有临床意义。
在马德里圣卡洛斯大学临床医院生殖免疫科，对一组来自单一参考中心的 RRF 女性患者进行 CD/NCGS 易感基因 HLA 研究，并评估无麸质饮食对生殖成功的影响。
对 173 例 RRF 患者进行了回顾性研究，这些患者均连续就诊于马德里圣卡洛斯大学临床医院的生殖免疫科。我们收集和分析了具有 CD 和 NCGS 相关 HLA 等位基因（HLA DQ2.2、DQ2.5、DQ8 和 DQ7.5）的 RRF 患者的临床、分析和免疫特征。
与普通人群相比（69%对 35%-40%，p<0.0001），我们的 RRF 队列中与 CD 和 NCGS 相关的 HLA 等位基因的患病率明显更高。仅有 2.3%的患者符合 CD 诊断标准。在我们的 RRF 队列中，CD/NCGS 的 HLA 遗传易感性（HLA-风险组）与无这些等位基因（HLA-阴性组）相比，甲状腺功能减退症的发生率显著更高（48.7%对 26.92%，p=0.03）。具有 CD/NCGS 和甲状腺疾病 HLA 遗传易感性的患者在后续妊娠管理后的妊娠成功率显著更高（55%对 30%，p=0.002）。在该组中发现两个因素具有显著意义：无麸质饮食（p=0.019）和左甲状腺素的使用（p=0.042）。
在我们的 RRF 患者队列中，与普通人群相比，我们观察到 CD/NCGS 的 HLA 易感基因的患病率明显更高，并且与甲状腺改变的发生率更高相关。无麸质饮食和甲状腺病理情况下使用左甲状腺素对妊娠结局有显著的有益影响。我们建议，在存在风险等位基因的情况下，对 CD/NCGS 进行 HLA 基因分型和无麸质饮食可以改善 RRF 患者的妊娠结局。
