Global report on primary immunodeficiencies: 2018 update from the Jeffrey Modell Centers Network on disease classification, regional trends, treatment modalities, and physician reported outcomes

Abstract

Primary immunodeficiencies (PI) are genetic defects of the immune system that result in chronic, serious, and often life-threatening infections, if not diagnosed and treated. Many patients with PI are undiagnosed, underdiagnosed, or misdiagnosed. In fact, recent studies have shown that PI may be more common than previously estimated and that as many as 1% of the population may be affected with a PI when all types and varieties are considered. In order to raise awareness of PI with the overall goal of reducing associated morbidity and mortality, the Jeffrey Modell Foundation (JMF) established a network of specialized centers that could better identify, diagnose, treat, and follow patients with PI disorders. Over the past decade, the Jeffrey Modell Centers Network (JMCN) has provided the infrastructure to accept referrals, provide diagnosis, and offer treatments. Currently, the network consists of 792 Expert Physicians at 358 institutions, in 277 cities, and 86 countries spanning 6 continents. JMF developed an annual survey for physician experts within the JMCN, using the categories and gene defects identified by the International Union of Immunological Societies Expert Committee for the Classification of PI, to report on the number of patients identified with PI; treatment modalities, including immunoglobulins, transplantation, and gene therapy; and data on gender and age. Center Directors also provided physician-reported outcomes and differentials pre- and post-diagnosis. The current physician-reported data reflect an increase in diagnosed patients, as well as those receiving treatment. Suspected patients are being identified and referred so that they can receive early and appropriate diagnosis and treatment. The significant increase in patients identified with a PI is due, in part, to expanding education and awareness initiatives, newborn screening, and the expansion of molecular diagnosis and sequencing. To our knowledge, this is the most extensive single physician report on patients with PI around the world.

Ataxia‐telangiectasia: A review of clinical features and molecular pathology

“…Ataxia‐telangiectasia is reported all over the world with an estimated prevalence of 1:40 000 to 1:100 000 . ATM deficiency is the second most common monogenic PID after familial Mediterranean fever with 2,514 globally reported patients (1,262 in North America, 251 in Latin America, 696 in Europe, 199 patients in Asia and Oceania, 106 patients in Africa) …”

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

“…Predominantly antibody deficiencies are the most frequent type of primary immunodeficiency disorders (PIDs), with more than 13,000 symptomatic patients registered globally (~20% of all reported PID patients to date) [2]. Selective immunoglobulin A deficiency (SIgAD), the most prevalent of PID, is characterized by decreased serum IgA level lower than 7 mg/dL in individuals older than 4 years with normal levels of IgM and IgG in serum and exclusion of other causes of hypogammaglobulinemia.…”

Primary Immunodeficiency

“…Individual type of PIDs is considered to be rare in the population; however, recent studies have shown that PIDs may be more common than previously estimated 1% of the population when all varieties are combined [5]. The prevalence of PIDs varies depending on the type of immunodeficiencies and is difficult to be precisely calculated as the number of diagnosed cases is rapidly increasing.…”

“…The prevalence of PIDs varies depending on the type of immunodeficiencies and is difficult to be precisely calculated as the number of diagnosed cases is rapidly increasing. A 2018 global survey from the Jeffrey Modell Centers Network (JMCN) reported the case of PID patients followed in the JMCN increased by 35.4% to 102,097, while the case of patients identified with a specific gene defect increased 21.8% to 67,308 during the same period [5]. Up to 2018, 354 distinct disorders with 344 different gene defects were recognized [6].…”

“…It is estimated that 70-90% of individuals living with a PID are undiagnosed [7], particularly in the area with poor medical condition and lacking laboratory resources. With the extensive application of exome or whole genome sequencing, it was predicted that the associated PID genetic defects would reach 1000 under current trend in next decade [5]. Table 1 listed the reported number of 18 most common PID defects among 354 inborn errors of immunity [5].…”