The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017

Shillitoe, Benjamin; Bangs, Catherine; Guzmán, David Sánchez-Migallón; Gennery, Andrew R.; Longhurst, Hilary; Slatter, Mary; Edgar, J. D. M.; Thomas, Moira; Worth, Austen; Huissoon, Aarnoud; Arkwright, Peter D.; Jolles, Stephen; Bourne, Helen; Alachkar, Hana; Savic, Sinisa; Kumararatne, Dinakantha; Patel, Smita Y.; Baxendale, Helen; Noorani, Sadia; Yong, Patrick; Waruiru, Catherine; Pavaladurai, V.; Kelleher, Peter; Herriot, Richard; Bernatonienne, J.; Bhole, Malini; Steele, Cathal; Hayman, Grant; Richter, Alex; Gompels, Mark; Chopra, Charu; Garcez, Tomaz; Buckland, Matthew

doi:10.1111/cei.13125

Cited by 65 publications

(83 citation statements)

References 21 publications

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“…1a ; Extended Data Table 1 ). This cohort represents a third of CVID and half of CID patients registered in the UK 9 . Clinical phenotypes were dominated by adult-onset sporadic AD-PID: all had recurrent infections, 28% had autoimmunity, and 8% had malignancy ( Fig.…”

Section: Patient Cohortmentioning

confidence: 99%

Whole-genome sequencing of a sporadic primary immunodeficiency cohort

Thaventhiran¹,

Allen²,

Burren³

et al. 2020

Nature

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169

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Primary immunodeficiency (PID) is characterised by recurrent and often life-threatening infections, autoimmunity and cancer, and it presents major diagnostic and therapeutic challenges. Although the most severe forms present in early childhood, the majority of patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent, and up to 10% develop lymphoid malignancies 1 – 3 . Consequently, in sporadic PID genetic diagnosis is difficult and the role of genetics is not well defined. We addressed these challenges by performing whole genome sequencing (WGS) of a large PID cohort of 1,318 participants. Analysis of coding regions of 886 index cases found disease-causing mutations in known monogenic PID genes in 10.3%, while a Bayesian approach (BeviMed 4 ) identified multiple potential new candidate genes, including IVNS1ABP . Exploration of the non-coding genome revealed deletions in regulatory regions which contribute to disease causation. Finally, a genome-wide association study (GWAS) identified PID-associated loci and uncovered evidence for co-localisation of, and interplay between, novel high penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to variable penetrance and phenotypic complexity in PID. Thus, a cohort-based WGS approach to PID diagnosis can increase diagnostic yield while deepening our understanding of the key pathways influencing human immune responsiveness.

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Section: Patient Cohortmentioning

confidence: 99%

Whole-genome sequencing of a sporadic primary immunodeficiency cohort

Thaventhiran¹,

Allen²,

Burren³

et al. 2020

Nature

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169

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“…The most frequent diseases of PIDs were CVID (36.3%), hereditary angioedema (8%) and agammaglobulinemia (5.4%). Consanguinity was reported at 2.9% and a genetic diagnosis was confirmed in 25.3% of the cohort [63][64][65]. Abuzakouk, et al at in 2005, registered separately 115 patients from 1996 to 2003 within a national registry for PIDs in the Republic of Ireland (higher than those in the ESID registry 2014 with 107 patients).…”

Section: Europementioning

confidence: 99%

Global systematic review of primary immunodeficiency registries

Abolhassani

Azizi

Sharifi

et al. 2020

Expert Review of Clinical Immunology

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Introduction: During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered: Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion: Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.

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“…The highest prevalence of CVID has been documented in the USA (40.2% of all PID patients), whilst the lowest rates were observed in the Middle East (2.6%) and Africa (1.3%) [12]. The most likely reasons for these differences are the availability of appropriate diagnostic methods and registry data and awareness of PID [13].…”

Section: Epidemiologymentioning

confidence: 99%

Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management

Yazdani¹,

Habibi²,

Sharifi³

et al. 2020

J Investig Allergol Clin Immunol

105

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Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by hypogammaglobulinemia and increased susceptibility to recurrent bacterial infections. It is the most frequent symptomatic antibody deficiency, with a wide variety of infectious and noninfectious complications. Numerous studies have demonstrated that immunological and genetic defects are involved in the pathogenesis of CVID. However, in most cases, the genetic background of the disease remains unidentified. This review aims to discuss various aspects of CVID, including epidemiology, pathogenesis, symptoms, diagnosis, classification, and management.

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The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017

Cited by 65 publications

References 21 publications

Whole-genome sequencing of a sporadic primary immunodeficiency cohort

Whole-genome sequencing of a sporadic primary immunodeficiency cohort

Global systematic review of primary immunodeficiency registries

Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management

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