Claire Bethune

• Medical Professional at University of Plymouth

Background Updated COVID-19 vaccines have been developed to help broaden protection against circulating SARS-CoV-2 variants. Here we present a 3-month interim analysis from a phase 3, randomized, observer-blind, active-controlled study of 2 omicron BA.1-containing vaccines: BA.1-monovalent mRNA-1273.529 (BA.1 variant only) and BA.1-bivalent mRNA-12...

The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator of Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified a novel heterozygous germline mutation STAT6 c.1255G > C, p.D419H leading to overactivity of IL-4 JAK/STAT si...

Background: The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and immunogenicity of omicron BA.1 monov...

Background Omicron-containing bivalent boosters are available worldwide. Results of a large, randomized, active-controlled study are presented. Methods This phase 3, randomized, observer-blind, active-controlled trial in the United Kingdom evaluated the immunogenicity and safety of 50-μg doses of omicron-BA.1-monovalent mRNA-1273.529 and bivalent...

Aims We investigated whether we could have a material and sustained impact on immunology test ordering by primary care clinicians by building evidence-based and explanatory algorithms into test ordering software. Methods A service evaluation revealed cases of over-requesting of antinuclear antibody, allergen-specific IgE and total IgE tests, and u...

Background: Granulomatous and lymphocytic interstitial lung disease (gl-ILD) is a major cause of morbidity and mortality among patients with common variable immunodeficiency. Corticosteroids are recommended as first-line treatment for gl-ILD, but evidence for their efficacy is lacking. Objective: We analyzed the effect of high-dose corticosteroi...

Background The Valneva COVID-19 vaccine (VLA2001; Valneva Austria, Vienna, Austria) is an inactivated whole-virus, adjuvanted SARS-CoV-2 vaccine. We aimed to assess the safety and immunogenicity of primary vaccination with VLA2001 versus the ChAdOx1-S (Oxford-AstraZeneca) adenoviral-vectored vaccine. Methods In this immunobridging phase 3 trial (C...

Background Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster do...

Background Individuals with primary and secondary immunodeficiency (PID/SID) were shown to be at risk of poor outcomes during the early stages of the SARS-CoV-2 pandemic. SARS-CoV-2 vaccines demonstrate reduced immunogenicity in these patients. Objectives To understand whether the risk of severe COVID-19 in individuals with PID or SID has changed...

Currently there is no guideline to support the use of immunoglobulin replacement therapy (IgRT) in primary and secondary immunodeficiency disorders in UK. The UK Primary Immunodeficiency Network (UK-PIN) and the British Society of Immunology (BSI) joined forces to address this need. Given the paucity of evidence a modified Delphi approach was emplo...

Background Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. Objectives To determine the immunogenicity of the third primary SARS-CoV-2...

Background Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood.ObjectivesCOVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response...

Background Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune respons...

Purpose The purpose of this phase 3 study was to evaluate the efficacy, pharmacokinetics (PK), and safety of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) in patients with primary immunodeficiency (PI). Methods Immunoglobulin treatment-experienced subjects with PI received 52 weeks of IGSC 20% given weekly...

Background Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. Objectives To determine the immunogenicity of the third primary SARS-CoV-2...

Many patients with immunodeficiencies require lifelong immunoglobulin replacement therapy (IgRT). In a multicenter, randomized, open-label, crossover, non-inferiority 3-month-trial, we compared the impact of the subcutaneous immunoglobulin Gammanorm® administered via pump or syringe (rapid push). Primary endpoint was the life quality index (LQI), s...

Background Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives COVID in patients with antibody deficiency (COV-AD) is a multi-site United Kingdom study that aims to determine the immu...

Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with reg...

The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified t...

Background The COVID-19 pandemic imposed multiple restrictions on healthcare services. Objective To investigate the impact of the pandemic on Allergy & Immunology (A&I) services in the UK. Methods National survey of all A&I services registered with the Royal College of Physicians and/or British Society for Allergy and Clinical Immunology. The sur...

Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable c...

Ten percent of the general population believe themselves allergic to beta-lactams, many erroneously. Alternative, broader spectrum antibiotics are associated with increased drug costs and colonization with resistant organisms. A point prevalence study of hospital inpatients determined the local reported rate of penicillin allergy, the nature of all...

Chronic norovirus infection (CNI) is increasingly recognised in immune compromised individuals. It is often identified in the context of a severe, persistent enteropathy. The significance of CNI is yet to be well defined and specific treatments are poorly characterised. We present data from a UK-wide, multicentre survey of CNI in patients with prim...

Background Hereditary angioedema with C1 inhibitor deficiency (C1‐INH‐HAE) is characterized by recurrent swelling in subcutaneous or submucosal tissues. Symptoms often begin by age 5–11 years and worsen during puberty, but attacks can occur at any age and recur throughout life. Disease course in elderly patients is rarely reported. Methods The Ica...

The use of regular infusions of immunoglobulin is well established as a treatment for patients with antibody deficiency and for patients requiring immunomodulation. Although efficacy is believed to be equivalent for the different immunoglobulin products, it is generally regarded as best practice not to switch from one product to another unless ther...

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function C...

Common variable immunodeficiency (CVID) represents a heterogeneous group of rare disorders. There is considerable morbidity and mortality as a result of non‐infectious complications and this presents clinicians with management challenges. Clinical guidelines to support the management of CVID are urgently required. The UK Primary Immunodeficiency Ne...

Background Hereditary angioedema (HAE) is a potentially life-threatening, bradykinin-mediated disease, often misdiagnosed and under-treated, with long diagnostic delays. There are limited real-world data on best-practice management of HAE in the UK. Objectives To characterize the clinical profile, management and outcomes of patients with HAE type...

Background: CARD11 encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to NF-κB, JNK, and mTORC1. Germline CARD11 mutations cause several distinct primary immune disorders in humans, including SCID (biallelic null mutations), B cell Expansion with NF-κB and T cell Anergy (BENTA; heterozygous,...

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (w...

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profou...

Background: The genetic cause of primary immunodeficiency disease (PID) carries prognostic information. Objective: We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource–Rare Diseases cohort. Methods: In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a no...

Background: Immunologists are increasingly being asked to assess patients with non-classical and secondary antibody deficiency to determine their potential need for immunoglobulin replacement therapy (IGRT). Immunoglobulin is a limited, expensive resource and no clear guidance exists for this broad patient group. The purpose of this survey is to e...

Aim To record the level of allergy teaching occurring in UK medical schools. The UK has experienced an ‘allergy epidemic’ during the last 3–4 decades. Previous government reviews have emphasised the importance of allergy education and training, treating common allergies in primary care with referral pathways to a specialist and the creation of regi...

Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohort...

Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohort...

Idiopathic hypogammaglobulinemia, including CVID, has a heterogeneous clinical phenotype. This study used data from the national UKPID registry to examine factors associated with adverse outcomes, particularly lung damage and malignancy. 801 adults labeled with idiopathic hypogammaglobulinemia and CVID aged 18 to 96 years from ten UK cities were re...

C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of disabling and potentially life-threatening angioedema. Here we present an updated 2014 United Kingdom consensus document for the management of C1 inhibitor-deficient patients, representing a joint venture between the United Kingdom Primary Immunodeficiency Network and...

This report summarizes the establishment of the first national online registry of primary immune deficency in the United Kingdom, the United Kingdom Primary Immunodeficiency (UKPID Registry). This UKPID Registry is based on the European Society for Immune Deficiency (ESID) registry platform, hosted on servers at the Royal Free site of University Co...

Results from a 16-question survey about self-administration of hereditary angioedema (HAE) therapy, administered in Europe, Canada and the USA, were used to guide discussion at an international HAE expert meeting. The aim was to capture information about current practice in self-administered HAE therapy in these countries, including self-administra...

Angioedema is characterized by localized swelling of subcutaneous tissues or mucosa of the upper respiratory or gastrointestinal tract. Laryngeal involvement may threaten airway patency and can be fatal if not addressed promptly. There are several distinct subtypes of angioedema, caused by different pathological processes involving a range of proin...

Currently in the United Kingdom (UK), there is a mismatch between limited financial resources and the large proportion of patients with suspected allergies actually being referred to specialist allergy clinics. To better understand the case mix of patients being referred, we audited referrals to a regional allergy service over an 8 year period.The...

Patients with hereditary angioedema may present to the emergency department (ED) with subcutaneous and submucosal swellings, the most important being the development of laryngeal oedema, which can rapidly obstruct the airways and cause death. The aim of this study was to establish whether local guidelines exist for the management of such patients a...

Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in...

Hereditary angioedema (C1 inhibitor deficiency, HAE) is associated with intermittent swellings which are disabling and may be fatal. Effective treatments are available and these are most useful when given early in the course of the swelling. The requirement to attend a medical facility for parenteral treatment results in delays. Home therapy offers...

We present a consensus document on the diagnosis and management of C1 inhibitor deficiency, a syndrome characterized clinically by recurrent episodes of angio-oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1 inhibitor function is reduced due to impaired transcription or production of non-functional protein. The diagnosis...

Adrenaline (epinephrine) is the recommended first line treatment for patients with anaphylaxis. This review discusses the safety and efficacy of adrenaline in the treatment of anaphylaxis in the light of currently available evidence. A pragmatic approach to use of adrenaline auto-injectors is suggested.

We report an audit of patients referred to our departments with suspected chronic fatigue focusing on the relative roles that clinical assessment and screening investigations played in the making offmal diagnoses. Methods: A Retrospective review of the notes of 73 new patients referred with possible chronic fatigue. The main outcome measures were c...

A patient with chronic granulomatous disease who was being treated with steroids was diagnosed with a soft tissue Scedosporium apiospermum infection. Despite extensive treatment with antifungals progression to involve solid tissue (bone) occurred. Treatment required an HLA matched bone marrow transplant, which led to complete clearance of the funga...

Senior house officers (SHOs) (n=78) at the start of their accident and emergency (A&E) post were given an anonymous five case history questionnaire, containing one case of true anaphylaxis, and asked to complete the medication they would prescribe. In the case of anaphylaxis, 100% would administer adrenaline (epinephrine) but 55% would do so by the...

This is a report of a case of Epstein-Barr virus (EBV) associated haemophagocytic syndrome in a 17 year old woman with antibody deficiency. For two years before this presentation, serology showed abnormally high titres to EBV early antigen, suggestive of persistent infection with EBV. She became acutely unwell with clinical features consistent with...

Common variable immunodeficiency (CVID) is not a homogeneous disease, as has become clear from recent scientific studies. This makes the interpretation of studies of clinical therapeutics difficult to assess and raises questions about historical case reports. The evidence for the optimum use of replacement immunoglobulin in CVID is reviewed. This t...

Common variable immunodeficiency (CVID) is not a homogeneous disease, as has become clear from recent scientific studies. This makes the interpretation of studies of clinical therapeutics difficult to assess and raises questions about historical case reports. The evidence for the optimum use of replacement immunoglobulin in CVID is reviewed. This t...

It is a common misconception that food allergy can cause a wide variety of symptoms. A population study in the English town of High Wycombe showed a perceived prevalence of food intolerance of almost 20%, but double blind food challenge (the definitive test) provided objective evidence of symptoms related to food in fewer than 2% of subjects. 1 Thi...

Apolipoprotein E (ApoE) has recently been proposed as an aetiological factor of Alzheimer's disease (AD): ApoE is co-localized to amyloid plaques and neurofibrillary tangles in the brain and binds to A beta-protein in vitro. An association of ApoE epsilon 4 allele with the development of AD has been reported. Islet amyloid is formed from islet amyl...