Zamani Raha, Zoghi Samaneh, Shahkarami Sepideh, Seyedpour Simin, Jimenez Heredia Raúl, Boztug Kaan, Rezaei Nima
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.
Endocr Metab Immune Disord Drug Targets. 2024;24(5):596-605. doi: 10.2174/0118715303263327230922043929.
Inborn errors of immunity are a growing group of disorders with a wide spectrum of genotypic and phenotypic profiles. CARMIL2 (previously named RLTPR) deficiency is a recently described cause of immune dysregulation, mainly presenting with allergy, mucocutaneous infections, and inflammatory bowel disease. CARMIL2 deficiency is categorized under diseases of immune dysregulation with susceptibility to lymphoproliferative conditions.
Here we describe a 29-years-old male from a consanguineous family, with food and sting allergy, allergic rhinitis, facial molluscum contagiosum (viral infection of the skin in the form of umbilicated papules), eosinophilia and highly elevated serum IgE level. Whole exome sequencing revealed numerous homozygous variants, including a CARMIL2 nonsense mutation, a gene regulating actin polymerization, and promoting cell protrusion formation.
The selective role of CARMIL2 in T cell activation and maturation through cytoskeletal organization is proposed to be the cause of immune dysregulation in individuals with CARMIL2 deficiency. CARMIL2 has an important role in immune pathways regulation, through cell maturation and differentiation, giving rise to a balance between Th1, Th2, and Th17 immune response. This case can improve the understanding of the different impacts of CARMIL2 mutations on immune pathways and further guide the diagnosis of patients with similar phenotypes.
遗传性免疫缺陷是一类日益增多的疾病，具有广泛的基因型和表型特征。CARMIL2（以前称为RLTPR）缺陷是最近描述的免疫失调原因，主要表现为过敏、皮肤黏膜感染和炎症性肠病。CARMIL2缺陷被归类为对淋巴细胞增殖性疾病易感的免疫失调疾病。
我们在此描述一名来自近亲家庭的29岁男性，患有食物和蜂蜇过敏、过敏性鼻炎、面部传染性软疣（以脐状丘疹形式出现的皮肤病毒感染）、嗜酸性粒细胞增多和血清IgE水平高度升高。全外显子组测序发现了许多纯合变异，包括一个CARMIL2无义突变，该基因调节肌动蛋白聚合并促进细胞突起形成。
CARMIL2通过细胞骨架组织在T细胞活化和成熟中的选择性作用被认为是CARMIL2缺陷个体免疫失调的原因。CARMIL2在免疫途径调节中具有重要作用，通过细胞成熟和分化，在Th1、Th2和Th17免疫反应之间实现平衡。该病例可增进对CARMIL2突变对免疫途径不同影响的理解，并进一步指导具有相似表型患者的诊断。
