Saghafi Shiva, Zandieh Fariborz, Fazlollahi Mohammad Reza, Glocker Cristina, Frede Natalie, Buchta Mary, Yang Linlin, Mahmoudi Amir Hossein, Houshmand Massoud, Pourpak Zahra, Grimbacher Bodo, Moin Mostafa
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Department of Asthma, Allergy, and Immunology, Bahrami Children Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Allergy Asthma Immunol. 2022 Jun 18;21(3):355-363. doi: 10.18502/ijaai.v21i3.9809.
Early diagnosis of primary immunodeficiencies is crucial for timely treatment and preventing unwanted complications. Next-generation sequencing (NGS) and detailed clinical and immunological evaluation can help early detect such disorders. This study aimed to confirm the diagnosis of two cases of autosomal recessive hyper-immunoglobulin E (IgE) syndrome (AR-HIES), presenting with irreversible eye involvement. Two unrelated patients with suspected AR-HIES were referred to the Immunology, Asthma and Allergy Research Institute (IAARI), Tehran, Iran. Immunological screening tests were performed for AR-HIES, which showed elevated serum IgE levels, eosinophilia, and low T-lymphocyte responses. NGS was performed, and the results were confirmed by Sanger sequencing. Sequence analysis showed a mutation in intron 17 of the dedicator of cytokinesis 8 (DOCK8) gene in the first patient, and a homozygous three base-pair deletion in exon 45 of DOCK8 in the second patient. This is the first time such mutations are reported and these variants are predicted to be damaging. Both patients suffered from persistent viral infections along with cytomegalovirus (CMV) retinitis. Suspicion of these two novel DOCK8 mutations can benefit patients presenting with recalcitrant ophthalmic viral involvements and relevant immunological test results. This would lead to earlier referrals for immunologic and genetic confirmation and thus, a more timely intervention with hematopoietic stem cell transplantation (HSCT).
原发性免疫缺陷的早期诊断对于及时治疗和预防不良并发症至关重要。新一代测序（NGS）以及详细的临床和免疫学评估有助于早期发现此类疾病。本研究旨在确诊两例常染色体隐性高免疫球蛋白E（IgE）综合征（AR-HIES），这两例患者均出现了不可逆的眼部病变。两名疑似患有AR-HIES的非亲属患者被转诊至伊朗德黑兰的免疫、哮喘与过敏研究所（IAARI）。针对AR-HIES进行了免疫学筛查测试，结果显示血清IgE水平升高、嗜酸性粒细胞增多以及T淋巴细胞反应低下。进行了NGS检测，并通过桑格测序对结果进行了确认。序列分析显示，首例患者的细胞分裂素8专一性蛋白（DOCK8）基因第17内含子存在突变，第二例患者的DOCK8基因第45外显子存在纯合性三个碱基对缺失。这是首次报告此类突变，且预计这些变异具有损害性。两名患者均患有持续性病毒感染以及巨细胞病毒（CMV）视网膜炎。怀疑这两种新的DOCK8突变可能对出现顽固性眼部病毒感染以及相关免疫学检测结果的患者有益。这将促使更早地转诊进行免疫学和遗传学确认，从而更及时地进行造血干细胞移植（HSCT）干预。
