Jeffrey Modell Foundation, New York, NY, United States.
Invitae, San Francisco, CA, United States.
Front Immunol. 2022 Jun 10;13:906540. doi: 10.3389/fimmu.2022.906540. eCollection 2022.
Genetic disorders that impair the immune system, known as Primary Immunodeficiencies (PI), include over 450 single-gene inborn errors of immunity. Timely and appropriate diagnosis and treatment is vital to quality of life (QOL) and sometimes survival, as patients are susceptible to frequent, persistent, severe, and sometimes life-threatening infections or autoimmunity. Suspected PI patients that do not have a genetic diagnosis often endure a prolonged, onerous, inefficient, and expensive experience, known as a diagnostic odyssey. The resulting diagnostic delay prohibits proper disease management and treatment, causing unnecessary distress and diminished QOL. Next-generation sequencing (NGS) offers relief from the distress of the diagnostic odyssey, but because of cost and barriers to access, it is regularly unobtainable. The Jeffrey Modell Foundation (JMF) introduced "Jeffrey's Insights", a no-charge genetic sequencing pilot program, in January 2019 for patients within the Jeffrey Modell Centers Network (JMCN) with an underlying PI, but no genetic diagnosis. Building on the success of the pilot program, JMF expanded it globally to more than 400 Centers in the JMCN in early 2020. The most current version of Invitae's PI Panel available was used for this program. All participating clinicians were invited to complete a brief questionnaire assessing prior impediments to access and post-sequencing alterations in disease management and treatment. A total of 1,398 patients were tested, with 20.3% receiving a molecular diagnosis and many more receiving helpful diagnostic leads. Results obtained from genetic sequencing led to an alteration of clinical diagnosis, disease management, treatment, and genetic counseling in 39%, 38%, 35%, and 53% of patients, respectively. The global expansion of this program further underscores the crucial need for NGS for PI, along with its efficiency and potential cost savings. The results of this program to date further define rationale for the availability of comprehensive diagnostic NGS for patients with PI when requisitioned by an expert immunologist.
遗传障碍会损害免疫系统，被称为原发性免疫缺陷（PI），包括超过 450 种单基因先天性免疫缺陷。及时和适当的诊断和治疗对生活质量（QOL）至关重要，有时甚至对生存至关重要，因为患者容易频繁、持续、严重，有时甚至危及生命的感染或自身免疫。没有遗传诊断的疑似 PI 患者通常会经历漫长、繁重、低效和昂贵的经历，即诊断之旅。由此产生的诊断延迟会妨碍适当的疾病管理和治疗，导致不必要的痛苦和生活质量下降。下一代测序（NGS）为诊断之旅的痛苦提供了缓解，但由于成本和获取障碍，它通常无法获得。杰弗里·莫德尔基金会（JMF）于 2019 年 1 月推出了“杰弗里洞察”，这是一项免费的基因测序试点计划，面向杰弗里·莫德尔中心网络（JMCN）内患有潜在 PI 但没有遗传诊断的患者。该试点计划取得成功后，JMF 于 2020 年初将其扩展到全球超过 400 个 JMCN 中心。该计划使用的是 Invitae 最新版本的 PI 面板。共有 1398 名患者接受了测试，其中 20.3%的患者获得了分子诊断，更多的患者获得了有帮助的诊断线索。基因测序结果导致 39%、38%、35%和 53%的患者临床诊断、疾病管理、治疗和遗传咨询发生改变。该计划在全球范围内的扩展进一步强调了 PI 进行 NGS 的迫切需要，以及它的效率和潜在的节省成本。该计划迄今为止的结果进一步明确了在专家免疫学家要求时为 PI 患者提供全面诊断 NGS 的合理性。
