Singh Neha, Ranganath Priya, Jayaram Ananthvikas, Jhawar Prerna, Kotecha Udhaya, Janardhanan Jyothi, Kumar Harish, Sudheer K A, Ali Syed Mohammed Naushad, Arigela Karthik, Ginigeri Chetan, Bhattad Sagar
Paediatric Immunology and Rheumatology Unit, Aster CMI Hospital, Bengaluru, India.
Clinical Genetics, Neuberg Center for Genomic Medicine, Ahmedabad, Gujarat, India.
Immunol Res. 2024 Dec 12;73(1):8. doi: 10.1007/s12026-024-09571-9.
DOCK8 deficiency is the most common cause of autosomal recessive hyper-IgE syndrome (AR-HIES). The clinical spectrum is wide resulting in combined immunodeficiency, atopy, autoimmunity, and malignancies. To study the clinical and molecular profile of 20 patients with DOCK8 deficiency. Four hundred and eight patients with various inborn errors of immunity (IEIs) were diagnosed in the Pediatric Immunology Unit of our hospital during the study period of February 2017 to August 2023. Based on the clinical and immunological phenotype, DOCK8 deficiency was suspected in 31 patients. Genetic studies confirmed DOCK8 deficiency in 20 patients, and their profile was analyzed in detail. Twenty patients from 17 kindreds were diagnosed with DOCK8 deficiency. The female-to-male ratio was 1.2:1. The mean age at onset of symptoms and diagnosis was 9.8 and 69.8 months, respectively. Thirteen out of 17 families (76%) reported consanguinity. Eczema was the presenting manifestation in 19 patients (95%). Mucocutaneous manifestations included oromucosal hyperpigmentation (n = 8), scalp seborrhoea (n = 2), psoriasis (n = 2), and alopecia (n = 1). The spectrum of infections included pneumonia (n = 14), otitis media (n = 6), gastrointestinal infections (n = 6), cutaneous viral infections (n = 5), oral candidiasis (n = 4), and meningoencephalitis (n = 2). Three patients had developed bronchiectasis. Four patients had autoimmune manifestations including autoimmune hemolytic anemia (n = 2) and vasculitis (n = 2). The whole exome sequencing showed deletions (8 kindreds) as the most common mutation in the DOCK8 gene. Overall, 11 of these mutations were novel. Ten patients were on monthly intravenous immunoglobulin therapy and antibiotic prophylaxis at the time of writing this paper. Three patients underwent hematopoietic stem cell transplants elsewhere, two of whom succumbed to post-transplant complications and one is doing well. Nine patients died during the study period. We present one of the largest single-center experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcomes in our cohort.
DOCK8缺陷是常染色体隐性高IgE综合征（AR-HIES）最常见的病因。其临床谱广泛，可导致联合免疫缺陷、特应性、自身免疫和恶性肿瘤。为研究20例DOCK8缺陷患者的临床和分子特征。在2017年2月至2023年8月的研究期间，我院儿科免疫科诊断了408例各种先天性免疫缺陷（IEIs）患者。根据临床和免疫表型，31例患者疑似DOCK8缺陷。基因研究证实20例患者存在DOCK8缺陷，并对其特征进行了详细分析。来自17个家族的20例患者被诊断为DOCK8缺陷。男女比例为1.2:1。症状出现和诊断时的平均年龄分别为9.8个月和69.8个月。17个家族中有13个（76%）有近亲结婚史。19例患者（95%）以湿疹为首发表现。皮肤黏膜表现包括口腔黏膜色素沉着（n = 8）、头皮脂溢性皮炎（n = 2）、银屑病（n = 2）和脱发（n = 1）。感染谱包括肺炎（n = 14）、中耳炎（n = 6）、胃肠道感染（n = 6）、皮肤病毒感染（n = 5）、口腔念珠菌病（n = 4）和脑膜脑炎（n = 2）。3例患者出现支气管扩张。4例患者有自身免疫表现，包括自身免疫性溶血性贫血（n = 2）和血管炎（n = 2）。全外显子测序显示缺失（8个家族）是DOCK8基因最常见的突变。总体而言，这些突变中有11个是新发现的。在撰写本文时，10例患者接受每月一次的静脉注射免疫球蛋白治疗和抗生素预防。3例患者在其他地方接受了造血干细胞移植，其中2例死于移植后并发症，1例情况良好。9例患者在研究期间死亡。我们展示了来自印度关于DOCK8缺陷的最大单中心经验之一。诊断的显著延迟导致我们队列中的不良结局。
