PDF(Pubmed)
Abstract：
Major Histocompatibility Complex Class II (MHC II) deficiency is a rare primary immunodeficiency disorder (PID) with autosomal recessive inheritance pattern. The outcome is almost fatal owing to delayed diagnosis and lacking of effective therapy. Therefore, prompt diagnosis, timely and effective treatment are critical. Here, we report a 117-day-old boy with diarrhea, cough, cyanosis and tachypnea who was failed to be cured by empiric antimicrobial therapy initially and progressed to severe pneumonia and respiratory failure. The patient was admitted to the pediatric intensive care unit (PICU) immediately and underwent a series of tests. Blood examination revealed elevated levels of inflammatory markers and cytomegalovirus DNA. Imaging findings showed signs of severe infection of lungs. Finally, the diagnosis was obtained mainly through next-generation sequencing (NGS). We found out what pathogenic microorganism he was infected via repeated conventional detection methods and metagenomic next-generation sequencing (mNGS) of sputum and bronchoalveolar lavage fluid (BALF). And his whole exome sequencing (WES) examination suggested that CIITA gene was heterozygous mutation, a kind of MHC II deficiency diseases. After aggressive respiratory support and repeated adjustment of antimicrobial regimens, the patient was weaned from ventilator on the 56th day of admission and transferred to the immunology ward on the 60th day. The patient was successful discharged after hospitalizing for 91 days, taking antimicrobials orally to prevent infections post-discharge and waiting for stem cell transplantation. This case highlights the potential importance of NGS in providing better diagnostic testing for unexplained infection and illness. Furthermore, pathogens would be identified more accurately if conventional detection techniques were combined with mNGS.
摘要：
主要组织相容性复合物II类（MHCII）缺乏症是一种罕见的原发性免疫缺陷性疾病（PID），具有常染色体隐性遗传模式。由于诊断延迟和缺乏有效的治疗，结果几乎是致命的。因此,及时诊断,及时有效的治疗至关重要。这里,我们报告了一个117天大的腹泻男孩，咳嗽,最初通过经验性抗菌治疗未能治愈的紫癜和呼吸急促，并发展为重症肺炎和呼吸衰竭。患者立即被送往儿科重症监护病房（PICU），并接受了一系列测试。血液检查显示炎症标志物和巨细胞病毒DNA水平升高。影像学检查结果显示肺部严重感染的迹象。最后,诊断主要通过下一代测序(NGS)获得.我们通过反复的常规检测方法和痰和支气管肺泡灌洗液（BALF）的宏基因组下一代测序（mNGS），发现了他感染的病原微生物。他的整个外显子组测序（WES）检查表明CIITA基因是杂合突变，一种MHCⅡ缺乏症。在积极的呼吸支持和反复调整抗菌方案后，患者于入院第56天脱离呼吸机,并于第60天转入免疫病房.患者住院91天后成功出院,口服抗菌药物以预防出院后的感染，并等待干细胞移植。该病例强调了NGS在为无法解释的感染和疾病提供更好的诊断测试方面的潜在重要性。此外，如果将常规检测技术与mNGS结合使用，则可以更准确地识别病原体。
