Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%).

Inborn Errors of Immunity on the Island of Ireland - a Cross-Jurisdictional UKPID/ESID Registry Report.

The epidemiology of inborn errors of immunity (IEI) in the Republic of Ireland was first published in 2005 but has not been updated since. IEI prevalence data from Northern Ireland was last published in 2018. Using data from the United Kingdom Primary Immune Deficiency (UKPID) and European Society for Immunodeficiencies (ESID) registries, we reviewed all registered cases of IEI affecting adult patients ≥ 18 years of age from the two largest immunology specialist centres in Northern Ireland and the Republic of Ireland, respectively and calculated the combined minimum adult prevalence of IEI on the island of Ireland for the first time.

Safety Evaluation of an Expedited Omalizumab Home Self-Administration Pathway.

Introduction The Northern Ireland Regional Immunology Service (NIRIS) has developed an expedited omalizumab home self-administration pathway to reduce face-to-face clinic attendance during the coronavirus disease 2019 (COVID-19) pandemic. This audit evaluates the safety of this pathway with a particular focus on anaphylaxis. Objectives This study aimed to retrospectively audit the records of 39 patients undertaking expedited home self-administration at NIRIS for complications, particularly emergency department attendance for anaphylaxis.

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement.

Multicentre experience of home omalizumab treatment for chronic spontaneous urticaria.

Introduction: Due to perceived risk of anaphylaxis, home treatment with omalizumab has been limited. Within the UK, most centres administer omalizumab in a hospital setting. However, the reported prevalence of anaphylaxis is low and in December 2018 home treatment became licensed.

Unexpected combination: DiGeorge syndrome and myeloperoxidase deficiency.

We report a case of a 3-year-old boy who presented with recurrent bacterial and fungal infections and a known diagnosis of partial DiGeorge (22q11.2 deletion) syndrome. The nature and severity of his infections were more than normally expected in partial DiGeorge syndrome with normal T-cell counts and T-cell proliferative response to phytohaemagglutinin.

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry.

Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in (APDS1) or (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses.

Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations.

Background: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder.

X-linked Inhibitor of Apoptosis Complicated by Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) and Granulomatous Hepatitis.

The X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency characterized by Epstein-Barr virus (EBV)-driven hemophagocytic lymphohistiocytosis (HLH), splenomegaly, and colitis. Here, we present, for the first time, granulomatous hepatitis and granulomatous and lymphocytic interstitial lung disease (GLILD) as manifestations of XIAP deficiency. We report successful treatment of GLILD in XIAP deficiency with rituximab and azathioprine and discuss the role of XIAP deficiency in immune dysregulation.

The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1.

Purpose: Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients.

Interleukin 6 blockade for hyperimmunoglobulin D and periodic fever syndrome.

Hyperimmunoglobulin D and periodic fever syndrome (HIDS) is a rare, autoinflammatory condition caused by mutations in the mevalonate kinase gene. There is no standard treatment for HIDS, and randomized controlled trials are lacking. Corticosteroids, colchicine, nonsteroidal anti-inflammatory drugs, statins, and cyclosporine are of limited efficacy in controlling this condition.

A rare cause of a common symptom, Anakinra is effective in the urticaria of Schnitzler Syndrome: a case report.

Introduction: Schnitzler Syndrome is an uncommon, inflammatory condition that presents with a constellation of chronic unremitting urticaria, fever, bone pain, arthralgia or arthritis, and a monoclonal IgM gammopathy. There is usually neutrophilia and raised inflammatory markers. Delayed diagnosis is common and treatment often unsuccessful.

Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts.

Objective: To determine and compare the prevalence of MSH6 (a mismatch repair gene) mutations in a cohort of families with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), and in an unselected cohort of endometrial cancer patients (EC).

Design: Two patient cohorts participated in the study. A cohort of HNPCC families who were known to the Regional Medical Genetics department, and an unselected cohort of patients with a history of EC.

Tuberous sclerosis complex: clinical features, diagnosis, and prevalence within Northern Ireland.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes on chromosomes 9 and 16 respectively. Diagnosis is based on clinical features but can be difficult as a result of variable phenotypic expression. With the advantage of mutation analysis in making a diagnosis of TSC, and improved identification of the associated clinical features, there have been few new data on its prevalence and on the proportion of cases due to new mutations.

Length of interdialytic interval influences serum calcium and phosphorus concentrations.

Background: Higher levels of serum phosphorus and calcium are associated with increased haemodialysis (HD) patient mortality. Both of these factors act synergistically to promote vascular smooth muscle differentiation to an osteoblast-like phenotype and subsequent vascular calcification. The aim of this study was to investigate the influence of interdialytic interval on serum levels, as well as the influence of oral calcium-based phosphate binder load on the magnitude of the observed differences.