Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Folkhälsan Research Center, Helsinki, Finland.
Front Immunol. 2018 Oct 25;9:2468. doi: 10.3389/fimmu.2018.02468. eCollection 2018.
Mutations in , encoding a non-coding RNA molecule, underlie cartilage-hair hypoplasia (CHH), a syndromic immunodeficiency with multiple pathogenetic mechanisms and variable phenotype. Allergy and asthma have been reported in the CHH population and some patients suffer from autoimmune (AI) diseases. We explored AI and allergic manifestations in a large cohort of Finnish patients with CHH and correlated clinical features with laboratory parameters and autoantibodies. We collected clinical and laboratory data from patient interviews and hospital records. Serum samples were tested for a range of autoantibodies including celiac, anti-cytokine, and anti-21-hydroxylase antibodies. Nasal cytology samples were analyzed with microscopy. The study cohort included 104 patients with genetically confirmed CHH; their median age was 39.2 years (range 0.6-73.6). Clinical autoimmunity was common (11/104, 10.6%) and included conditions previously undescribed in subjects with CHH (narcolepsy, psoriasis, idiopathic thrombocytopenic purpura, and multifocal motor axonal neuropathy). Patients with autoimmunity more often had recurrent pneumonia, sepsis, high immunoglobulin (Ig) E and/or undetectable IgA levels. The mortality rates were higher in subjects with AI diseases ( = 14.056, = 0.0002). Several patients demonstrated serum autoantibody positivity without compatible symptoms. We confirmed the high prevalence of asthma (23%) and allergic rhinoconjunctivitis (39%). Gastrointestinal complaints, mostly persistent diarrhea, were also frequently reported (32/104, 31%). Despite the history of allergic rhinitis, no eosinophils were observed in nasal cytology in five tested patients. AI diseases are common in Finnish patients with CHH and are associated with higher mortality, recurrent pneumonia, sepsis, high IgE and/or undetectable IgA levels. Serum positivity for some autoantibodies was not associated with clinical autoimmunity. The high prevalence of persistent diarrhea, asthma, and symptoms of inflammation of nasal mucosa may indicate common pathways of immune dysregulation.
编码非编码 RNA 分子的基因突变是软骨毛发发育不良（CHH）的基础，这是一种具有多种发病机制和可变表型的综合征免疫缺陷。在 CHH 人群中已经报道了过敏和哮喘，一些患者患有自身免疫性（AI）疾病。我们探索了芬兰大型 CHH 患者队列中的 AI 和过敏表现，并将临床特征与实验室参数和自身抗体相关联。我们从患者访谈和医院记录中收集了临床和实验室数据。血清样本用于测试一系列自身抗体，包括乳糜泻、抗细胞因子和抗 21-羟化酶抗体。通过显微镜分析鼻细胞学样本。研究队列包括 104 名经基因证实的 CHH 患者；他们的中位年龄为 39.2 岁（范围 0.6-73.6）。临床自身免疫很常见（11/104，10.6%），包括以前在 CHH 患者中未描述的疾病（发作性睡病、银屑病、特发性血小板减少性紫癜和多灶性运动轴索性神经病）。自身免疫患者更常发生复发性肺炎、败血症、高免疫球蛋白（Ig）E 和/或无法检测到 IgA 水平。AI 疾病患者的死亡率更高（ = 14.056， = 0.0002）。一些患者表现出血清自身抗体阳性而无相符的症状。我们证实哮喘（23%）和过敏性鼻结膜炎（39%）的患病率较高。胃肠道投诉，主要是持续性腹泻，也经常报告（32/104，31%）。尽管有过敏性鼻炎病史，但在五个测试患者中，鼻细胞学中未观察到嗜酸性粒细胞。AI 疾病在芬兰 CHH 患者中很常见，与更高的死亡率、复发性肺炎、败血症、高 IgE 和/或无法检测到 IgA 水平相关。一些自身抗体的血清阳性与临床自身免疫无关。持续性腹泻、哮喘和鼻黏膜炎症症状的高患病率可能表明免疫失调的常见途径。
