背景:先天性免疫错误是一类越来越多的疾病,具有广泛的基因型和表型特征。CARMIL2(以前称为RLTPR)缺乏症是最近描述的免疫失调的原因,主要表现为过敏,皮肤粘膜感染,和炎症性肠病.CARMIL2缺乏被归类为免疫失调的疾病,具有对淋巴增生性病症的易感性。
方法:这里我们描述了一个来自近亲家庭的29岁男性,食物和刺痛过敏,过敏性鼻炎,面部传染性软体动物(以脐带丘疹形式的皮肤病毒感染),嗜酸性粒细胞增多和血清IgE水平高度升高。全外显子组测序揭示了许多纯合变体,包括CARMIL2无意义突变,调节肌动蛋白聚合的基因,促进细胞突起形成。
结论:CARMIL2在通过细胞-骨骼组织的T细胞活化和成熟中的选择性作用被认为是CARMIL2缺乏个体免疫失调的原因。CARMIL2在免疫通路调节中具有重要作用,通过细胞成熟和分化,在Th1、Th2和Th17免疫应答之间产生平衡。该病例可提高对CARMIL2突变对免疫通路不同影响的认识,进一步指导表型相似患者的诊断。
BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: 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.