Late-onset combined immunodeficiency

晚发型联合免疫缺陷
  • 文章类型: Case Reports
    染色体18q缺失综合征患者通常会出现低球蛋白血症。在这里,我们描述了两名染色体18q缺失综合征患者,他们表现为迟发性联合免疫缺陷(LOCID),以前没有报道过。患者1是一名29岁的男性,患有18q缺失综合征,他在Yamabiko医疗福利中心接受了26年的严重运动和智力残疾管理。虽然病人几乎没有感染,他在28岁时患上了肺孢子虫肺炎。患者2,一名48岁的女性,患有智力残疾和先天性畸形,被转诊到东京医学牙科大学医院,在她的胸部X线片上发现了异常的双侧肺部阴影。计算机断层扫描显示多发性淋巴结病和肺炎。腹股沟区淋巴结活检显示肉芽肿性淋巴结炎,染色体检查显示18q缺失。基于阵列的基因组杂交分析显示,患者1在18q21.32-q22.3缺失,患者2在18q21.33-qter缺失。两名患者的免疫状态检查显示全球蛋白血症,记忆B细胞和初始CD4+和/或CD8+细胞的数量减少,减少对羧基荧光素二乙酸酯琥珀酰亚胺酯T细胞分裂试验的反应,低水平的T细胞受体重组切除圈和Igκ缺失重组切除圈。因此,两名患者均被诊断为LOCID.尽管18q缺失综合征患者通常会出现体液免疫缺陷,这种疾病可以进一步复杂化的细胞介导的免疫缺陷,导致联合免疫缺陷。因此,18q缺失综合征患者应定期进行细胞/体液免疫能力检测.
    Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4+ and/or CD8+ cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.
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  • 文章类型: Review
    对常见可变免疫缺陷性疾病(CVID)的理解还在进化中。CVID以前是排除的诊断。新的诊断标准允许以更高的精度识别疾病。随着下一代测序(NGS)的出现,很明显,越来越多的CVID表型患者具有致病的遗传变异.如果发现了致病变异,这些患者被排除在CVID的总体诊断之外,并被认为患有CVID样疾病.在血缘关系更普遍的人群中,大多数患有严重原发性低丙种球蛋白血症的患者会有潜在的先天免疫错误,通常是早发性常染色体隐性遗传疾病。在非近亲社会,在大约20%~30%的患者中发现了致病变异.这些通常是常染色体显性突变,具有可变的外显率和表达能力。为了增加CVID和CVID样疾病的复杂性,一些遗传变异,如TNFSF13B(跨膜激活钙调节剂亲环蛋白配体相互作用剂)易感,或增强,疾病严重程度。这些变体不是致病的,但可以具有与更有害的突变的上位性(协同性)相互作用以恶化疾病严重程度。这篇综述描述了当前对与CVID和CVID样疾病相关的基因的理解。这些信息将帮助临床医生在调查具有CVID表型的患者的疾病的遗传基础时解释NGS报告。
    The understanding of common variable immunodeficiency disorders (CVID) is in evolution. CVID was previously a diagnosis of exclusion. New diagnostic criteria have allowed the disorder to be identified with greater precision. With the advent of next-generation sequencing (NGS), it has become apparent that an increasing number of patients with a CVID phenotype have a causative genetic variant. If a pathogenic variant is identified, these patients are removed from the overarching diagnosis of CVID and are deemed to have a CVID-like disorder. In populations where consanguinity is more prevalent, the majority of patients with severe primary hypogammaglobulinemia will have an underlying inborn error of immunity, usually an early-onset autosomal recessive disorder. In nonconsanguineous societies, pathogenic variants are identified in approximately 20% to 30% of patients. These are often autosomal dominant mutations with variable penetrance and expressivity. To add to the complexity of CVID and CVID-like disorders, some genetic variants such as those in TNFSF13B (transmembrane activator calcium modulator cyclophilin ligand interactor) predispose to, or enhance, disease severity. These variants are not causative but can have epistatic (synergistic) interactions with more deleterious mutations to worsen disease severity. This review is a description of the current understanding of genes associated with CVID and CVID-like disorders. This information will assist clinicians in interpreting NGS reports when investigating the genetic basis of disease in patients with a CVID phenotype.
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