Boyle JM, Buckley RH. J Clin Immunol . 2007;27(5):497–502 PURPOSE OF THE STUDY. To measure the prevalence of primary immunodeficiency diseases (PIDs) in the United States. STUDY POPULATION. A random sample of 10 005 American households (26 657 people) was included in the study. METHODS. Households were selected by random-digit dialing stratified according to time zone. Calls were placed by trained interviewers with computer assistance. Eighty percent of the households contacted completed the interview. Respondents were asked, “Has anyone in your household ever been diagnosed with a primary immunodeficiency disease such as common variable immunodeficiency, IgA [immunoglobulin A] deficiency, IgG subclass deficiency, or any other immunodeficiency? (This is not acquired immunodeficiency—AIDS).” If they replied “yes,” they were further questioned with details of the diagnosis and limited demographic information about the affected individual(s). RESULTS. Twenty-three individuals in 18 households were identified as having a specific PID (including common variable immunodeficiency, IgA deficiency, IgG subclass deficiency, X-linked agammaglobulinemia, severe combined immunodeficiency, and chronic granulomatous disease). The calculated prevalence of diagnosed immunodeficiency was 1 in 2000 children, 1 in 1200 people of all ages, and 1 in 600 households. The 95% confidence limits for the estimate for all individuals were between 1 in 824 and 1 in 1956. Several of the identified individuals with primary immunodeficiency were not receiving therapy that is standard of care for their diagnoses (γ-globulin replacement). CONCLUSIONS. Quoting the authors, “The current study suggests that these conditions are sufficiently common that primary care physicians are likely to see patients with underlying primary immunodeficiency disorders in their practice and should test for these disorders in patients with recurring, unusual or serious infections. In the absence of routine screening, physician awareness of the relative frequency of these disorders is critical to early diagnosis and treatment.” REVIEWER COMMENTS. This is an extremely important message for all primary care physicians. These patients are in your practices now. The authors also pointed out that several studies have shown that many cases of PID are diagnosed late or are “mild” enough that they are never diagnosed and that patients suffer excess morbidity and mortality as a result. Some severe cases may be missed because children die before they are diagnosed. Thus, the true prevalence of PID is likely to be higher than what was found in this study. I found it discouraging that two thirds of the people who should have been receiving γ globulin were not.

https://pediatrics.aappublications.org/content/pediatrics/122/Supplement_4/S224.2.full.pdf

Population Prevalence of Diagnosed Primary Immunodeficiency Diseases in the United States

http://grumach.com/wp-content/uploads/2014/08/Are-Complement-def-rare1.pdf

Are complement deficiencies really rare? Overview on prevalence, clinical importance and modern diagnostic approach.

Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency. Although more patients with SIgAD are asymptomatic, selected patients suffer from different clinical complications such as pulmonary infections, allergies, autoimmune diseases, gastrointestinal disorders and malignancy. Pathogenesis of SIgAD is still unknown; however, a defective terminal differentiation of B cells and defect in switching to IgA-producing plasma cells are presumed to be responsible. Furthermore, some cytogenic defects and monogenic mutations are associated with SIgAD. There is no specific treatment for patients with symptomatic IgA deficiency, although prophylactic antibiotic therapy along with circumstantial immunoglobulin replacement with justification and supportive care (using a product that contains minimal IgA) could be helpful for patients with a severe phenotype. The epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis, management and treatment in patients with SIgAD have been reviewed.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/sji.12499

Selective IgA Deficiency: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management

Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency.

The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013–2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

/pdf/fourth-update-on-the-iranian-national-registry-of-primary-3vitou0v3y.pdf

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis

Background Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers. Methods This study presents the demographic data and clinical manifestations of Iranian PID patients who were

Najmedin Kalantari

Papers

Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry.