Immunomonitoring and Microbiome Analysis in Alopecia Areata Patients Undergoing Fecal Microbiota Transplantation

摘要 斑秃（AA）影响多达680万人在美国和1.47亿世界各地，与终身 风险为2.1%，使其成为最常见的自身免疫性疾病之一。AA会导致严重的毁容， 对受影响的个人造成心理困扰，并在所有皮肤中承担最高的情感负担之一 疾病，特别是儿童和青少年，他们的自我形象与他们的外表密切相关。 目前，预后是不可预测的，没有FDA批准的AA治疗。AA显示几个 与其他自身免疫性疾病的遗传和免疫病理相似性，表明类似的 环境触发因素以及炎症反应导致终末器官毛囊损伤 (HF)可能有共同的机制。虽然我们的团队和其他人已经在 了解AA的遗传结构，AA中全身性自身免疫反应的环境触发因素， 尚未确定AA。因此，我们最近将注意力转向确定潜在的环境 特别是微生物组。在我们的初步研究中，我们分析了肠道微生物组的组成， 26名AA患者和10名健康受试者的队列研究，并发现组成 AA患者和健康对照组的肠道微生物组。我们观察到， AA患者中厚壁菌和类杆菌代表性不足，在其他研究中也发现了这一发现。 自身免疫性疾病我们对已建立的AA C3 H/HeJ小鼠模型的额外初步研究 证明了用广谱抗生素鸡尾酒进行预处理可以在 皮肤移植，表明肠道微生物组是AA发作所需的。此外，还有三起案件 在文献中报告的慢性斑秃/普秃患者， 微生物群移植（FMT）用于不相关的条件，随后经历了显着的头发再生。 综上所述，这些发现表明肠道微生物组在斑秃中的作用出乎意料， 提供了这项辅助研究资助的母研究的基本原理，题为“粪便微生物群 移植作为斑秃患者的潜在治疗方法。本辅助研究的目的 格兰特将在接受FMT的AA患者中进行微生物组分析和免疫学研究， 了解环境因素的致病作用，如肠道组成的变化 微生物组，通过FMT逆转AA。

ABSTRACT Alopecia areata (AA) affects as many as 6.8 million people in the U.S. and 147 million worldwide, with a lifetime risk of 2.1%, making it one of the most common autoimmune diseases. AA causes significant disfigurement and psychological distress to affected individuals and carries one of the highest emotional burdens amongst all skin diseases, particularly among children and adolescents whose self-image is so closely linked to their appearance. At present, the prognosis is unpredictable and there is no FDA approved treatment for AA. AA shows several genetic and immunopathogenic similarities to other autoimmune conditions, suggesting that similar environmental triggers as well as the inflammatory responses leading to damage in the end-organ, the hair follicle (HF), may have common mechanisms. While our group and others have made significant advances in understanding the genetic architecture of AA, the environmental triggers of systemic autoimmune response in AA have not been identified. Therefore, we recently turned our attention to determining potential environmental triggers, in particular, the microbiome. In our Preliminary Studies we analyzed the gut microbiome composition of a cohort of 26 AA patients and 10 healthy subjects, and found striking dissimilarities between the composition of the gut microbiome of AA patients and those of healthy controls. We observed an overrepresentation of firmicutes and an underrepresentation of bacteroides in AA patients, findings which are also seen in other autoimmune diseases. Our additional Preliminary Studies on the well-established C3H/HeJ mouse model of AA demonstrated that pre-treatment with a wide-spectrum antibiotic cocktail results in protection against AA after skin grafting, suggesting the gut microbiome is required for the onset of AA. In addition, three cases have been reported in the literature of patients with chronic alopecia areata/universalis who were treated with a fecal microbiota transplant (FMT) for unrelated conditions, who subsequently experienced significant regrowth of hair. Taken together, these findings suggest an unexpected role of the gut microbiome in alopecia areata, and provided the rationale for the Parent Study of this Ancillary Studies Grant, entitled “Fecal Microbiota Transplantation as a Potential Treatment for Patients with Alopecia Areata”. The purpose of this Ancillary Studies grant is to conduct microbiome analysis and immunological studies in AA patients undergoing FMT, in order to understand the pathogenic role of environmental factors, such as changes in the composition of the gut microbiome, in the reversal of AA by FMT.