天生的免疫错误(IEI)是一组异质性的遗传缺陷的免疫,主要由于传染性和非传染性并发症而导致儿童的高发病率和死亡率。在中等收入和低收入地区的国家中,IEI负担被严重低估了,这些地区的大多数IEI患者缺乏分子诊断。
我们分析了临床,免疫学,来自中东和北非(MENA)地区22个国家的IEI患者的遗传数据。数据来自国家注册和不同的数据库,如亚太免疫缺陷学会(APSID)注册,非洲免疫缺陷学会(ASID)注册,JeffreyModell基金会(JMF)注册,J项目中心,国际免疫缺陷协会(ICID)中心。
我们确定了17,120名IEI患者,其中女性占39.4%。60.5%的病例存在父母血缘关系,27.3%的患者来自先前已确认IEI家族史的家庭。患者发病时的中位年龄为36个月,中位诊断延迟为41个月。注册IEI患者的比率在每100,000人0.02至7.58之间,最低的是残疾调整寿命年(DALY)和儿童死亡率最高的国家。主要的抗体缺乏是在该队列的41.2%中诊断出的最常见的IEI实体。在经过基因评估的5871名患者中,诊断率为83%,大多数(65.2%)具有常染色体隐性缺陷.非综合征性联合免疫缺陷患者的死亡率最高(51.7%,中位年龄:3.5岁),特别是在与该表型相关的特定基因突变的患者中(RFXANK,RAG1和IL2RG)。
这个全面的注册中心强调了对MENA地区IEI患者进行详细调查的重要性。该地区IEI基因诊断的高产率对预防,预后,治疗,和资源分配。
Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis.
We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers.
We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG).
This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation.