Faculty of Medicine, Department of Pediatric Allergy and Immunology, Istanbul Medeniyet University, Istanbul, Turkey.
Faculty of Medicine, Department of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.
J Clin Immunol. 2024 Sep 16;45(1):9. doi: 10.1007/s10875-024-01791-w.
Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease.
Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cT) cells, and T-cell proliferation were analyzed.
Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the T2-like skewing accompanied by reduced T17-like responses was observed in cT and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs.
The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.
免疫调节、多内分泌腺病、肠病、X 连锁综合征（IPEX）是一种由致病性 FOXP3 变异引起的罕见自身免疫性疾病，具有多种临床表现，包括早发性糖尿病、湿疹和肠病。非典型病例表现出较轻的症状和独特的体征，需要不同的治疗方法。因此，在 IPEX 的准确诊断和管理方面存在一些模糊之处。我们旨在介绍 12 例 IPEX 患者的临床、遗传和免疫学评估结果，这些患者接受了长期随访，以帮助诊断和管理该疾病。
随着时间的推移，收集了患者的临床发现和治疗选择。分析了淋巴细胞亚群、蛋白表达、调节性 T（Treg）和循环滤泡辅助 T（cT）细胞以及 T 细胞增殖。
主要表现包括自身免疫（91.6%）、生长迟缓（66.7%）和湿疹（58.3%）。有 4 例经典和 8 例非典型 IPEX 个体。非典型患者更常见过敏表现。值得注意的是，慢性腹泻的严重程度比其他表现更为严重。有 4 例患者（33.3%）表现出嗜酸性粒细胞增多，9 例患者（75%）表现出高血清 IgE 水平。大多数患者表现出正常百分比的 Treg 细胞，伴有 CD25、FOXP3 和 CTLA-4 表达减少，但在造血干细胞移植（HSCT）后得到纠正。与健康对照组相比，患者的 cT 和 Treg 细胞中观察到 T2 样偏向，伴有 T17 样反应减少。总体而言，9 例患者（75%）接受了免疫抑制剂（IS）治疗，6 例（50%）接受了 HSCT，这是唯一一种能够持续控制疾病的治疗方法。6 例患者使用了西罗莫司，其控制效果优于其他 IS。
这是土耳其首例具有长期随访结果的队列研究，比较了典型和非典型病例，为不同治疗方式的结果和 IPEX 综合征中 T 细胞亚型变化提供了见解。
