Primary immunodeficiencies worldwide: an updated overview from the Jeffrey Modell Centers Global Network

Abstract

Primary immunodeficiencies (PI) are defects of the immune system that cause severe, sometimes life-threatening, infections if not diagnosed and treated appropriately. Many patients with PI are undiagnosed, under-diagnosed, or misdiagnosed. To raise awareness and assure earliest diagnosis, appropriate treatment, and proper care management, the Jeffrey Modell Foundation (JMF) implemented a physician education and public awareness program beginning in 2003. Data are requested annually from physician experts within the Jeffrey Modell Centers Network (JMCN), consisting of 602 expert physicians, at 253 academic institutions, in 206 cities, and 84 countries spanning six continents. Center Directors reported on patients' specific PI defects and treatment modalities including immunoglobulins, transplantation, and gene therapy as well as data on gender and age. Center Directors also provided physician-reported patient outcomes as well as pre- and post-diagnosis differences. Costs were assigned to these factors. In collaboration with the Network, JMF advocated, funded, and implemented population-based newborn screening for severe combined immunodeficiency and T cell lymphopenia, covering 96.2 % of all newborns in the US. Finally, 21 JMF Centers participated in a polio surveillance study of patients with PI who either received or have been exposed to the oral polio vaccine. These initiatives have led to an overall better understanding of the immune system and will continue to improve quality of life for those with PI.

Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

“…Approximately 2% of the studied PID patients excreted poliovirus. PID survival rates are improving in lower and middle income countries (22). Furthermore, iVDPV excreters are being identified at a markedly increased rate due to improved surveillance that includes polio symptom-free excreters (3).…”

Genes associated with common variable immunodeficiency: one diagnosis to rule them all?

“…Biallelic and monoallelic loss-of-function variants in TNFRSF13B have been registered in at least 2147 patients based on the Jeffrey Modell Centers Global Network report 1. Biallelic TNFRSF13B variants have always been associated with some degree of antibody deficiency,6 7 19 20 23–27 except for a homozygous C104R variant in a 25-year-old member of a CVID-affected family who was asymptomatic and had normal Ig levels at the time of the study 24.…”

“…Common variable immunodeficiency (CVID) is one of the most prevalent primary immunodeficiencies (PIDs) with an important morbidity and high number of medical encounters 1 2. According to the international consensus statement, CVID is defined by a marked decrease in serum IgG, decreased IgM and/or IgA, poor antibody responses to vaccines, and exclusion of defined causes of hypogammaglobulinaemia 2.…”

Efficacy, Safety, and Pharmacokinetics of a Novel Human Immune Globulin Subcutaneous, 20 % in Patients with Primary Immunodeficiency Diseases in North America

“…Patients with PIDD are susceptible to bacterial, viral, and fungal infections [2]. In about 53 % of these patients, the diagnosis of PIDD is associated with defective antibody production with or without decreased levels of serum immunoglobulin (Ig) (e.g., common variable immunodeficiency, specific antibody deficiency, X-linked or autosomal recessive agammaglobulinemia, hyper IgM syndrome) [3]. …”