Anti-MDA5 positivity: describing the frequency and spectrum of clinically evident MDA5 disease.

To evaluate experience in a tertiary rheumatology service with melanoma differentiation-association-protein-5 (MDA5) disease and testing, patients with positive autoantibody results were reviewed for the presence of clinical disease. Anti-MDA5 positivity was detected in 2% of myositis-specific antibody tests. Of these, 29% did not have features consistent with anti-MDA5 disease.

The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR.

Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.

Background: In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD.

Methods: Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD.

Combined immunodeficiency and impaired PI3K signaling in a patient with biallelic LCP2 variants.

Background: Inborn errors affecting components of the T-cell receptor signaling cascade cause combined immunodeficiency with various degrees of severity. Recently, homozygous variants in LCP2 were reported to cause pediatric onset of severe combined immunodeficiency with neutrophil, platelet, and T- and B-cell defects.

Objective: We sought to unravel the genetic cause of combined immunodeficiency and early-onset immune dysregulation in a 26-year-old man who presented with specific antibody deficiency, autoimmunity, and inflammatory bowel disease since early childhood.

Utility of repeat extractable nuclear antigen antibody testing: a retrospective audit.

Objectives: Autoantibodies to ENA are frequently ordered during the workup of suspected autoimmune connective tissue diseases. There are no current guidelines for repeat test ordering. The objective of this study was to assess the utility of repeat ENA testing after an initial negative result.

Frequency and Clinical Utility of Antibodies to Extractable Nuclear Antigen in the Setting of a Negative Antinuclear Antibody Test.

Objective: Simultaneous antibody testing during screening for autoimmune conditions is discouraged. The incidence of positive extractable nuclear antigen (ENA) in the setting of a negative antinuclear antibody (ANA) has been reported as low. Our objective was to characterize the frequency of diagnosis of new ANA-associated rheumatic disease (AARD) in the setting of a negative ANA with a positive ENA.

Missed Opportunities? A Retrospective Study Into Adults Hospitalized With Invasive Infection From Airway Pathogens.

Background: Invasive disease caused by airway pathogens, including , , , and , has high morbidity and mortality worldwide, with immunodeficiency being a known association with recurrent disease. The study aimed to describe the frequency of known immunodeficiency and predisposing factors in adult patients presenting with invasive infections and determine the frequency of screening for and detection of immunodeficiency.

Methods: A retrospective analysis was conducted at a large tertiary Australian health service, comprising multiple centers.

Congenital asplenia study: clinical and laboratory characterisation of adults with congenital asplenia.

Congenital asplenia is a rare disorder commonly associated with other visceral and cardiac congenital anomalies. Isolated congenital asplenia is even less common than syndromic forms. The risk of severe bacterial infections associated with asplenia is the most concerning clinical implication and carries a significant mortality risk.

Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia.

Objectives: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration.

Methods: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018).

masquerading as possible gamma-delta T-cell lymphoma in a paediatric patient with 22q11.2 deletion syndrome.

A 14-year-old boy with 22q11.2 deletion syndrome and a right ventricular to pulmonary artery xenograft conduit presented to an Australian tertiary children's hospital with prolonged fevers, weight loss, splenomegaly and a high proportion of gamma-delta T cells in peripheral blood and bone marrow, concerning for possible gamma-delta T-cell lymphoma. However, investigations did not reveal evidence of lymphoma or autoimmune disease.

Macrophage and neutrophil death programs differentially confer resistance to tuberculosis.

Apoptosis can potently defend against intracellular pathogens by directly killing microbes and eliminating their replicative niche. However, the reported ability of Mycobacterium tuberculosis to restrict apoptotic pathways in macrophages in vitro has led to apoptosis being dismissed as a host-protective process in tuberculosis despite a lack of in vivo evidence. Here we define crucial in vivo functions of the death receptor-mediated and BCL-2-regulated apoptosis pathways in mediating protection against tuberculosis by eliminating distinct populations of infected macrophages and neutrophils and priming T cell responses.

Underutilised human immunodeficiency virus testing in the setting of invasive pneumococcal disease.

People living with human immunodeficiency virus (HIV) are at increased risk of invasive pneumococcal disease (IPD). We assessed whether patients with invasive Streptococcus pneumoniae, in blood or cerebrospinal fluid, underwent HIV serology testing over a 5-year period. We found that only 39 inpatients out of 156 (25%) with IPD were tested for HIV and thus conclude that such testing is not being undertaken according to some guidelines in patients with IPD.

Pediatric Staphylococcus aureus Bacteremia: Clinical Spectrum and Predictors of Poor Outcome.

Background: Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood.

Methods: ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia (SAB) in children hospitalized in Australia and New Zealand over 24 months (2017-2018).

Exploring the Intersection of Isolated-CNS Hemophagocytic Lymphohistiocytosis and Pediatric Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids.

CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an extremely rare neurologic inflammatory condition. Fewer than 10 pediatric cases have been described.Debate persists as to whether it is a distinct disease or a clinical, radiologic, and histologic phenotype evolving into another disorder.

Influenza-specific IgG1 memory B-cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency.

Background: Annual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and receive immunoglobulin replacement therapy (IgRT), it remains unclear whether they can mount an antigen-specific response.

Objective: To quantify and characterise the antigen-specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination.

Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency.

Predominantly antibody deficiency (PAD) is the most prevalent form of primary immunodeficiency, and is characterized by broad clinical, immunological and genetic heterogeneity. Utilizing the current gold standard of whole exome sequencing for diagnosis, pathogenic gene variants are only identified in less than 20% of patients. While elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis, many other genes may remain as yet undefined to enable definitive diagnosis, prognostic monitoring and targeted therapy of patients.

Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in .

The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections.

Utility of repeated antinuclear antibody tests: a retrospective database study.

Background: Anti-nuclear antibody (ANA) testing is frequently used as a diagnostic or screening test in patients with inflammatory or musculoskeletal symptoms. The value of repeat testing is unclear. We sought to evaluate the frequency, utility, and cost of repeat ANA testing.

Multicenter Australian Study to Determine Criteria for Low- and High-Risk Penicillin Testing in Outpatients.

Background: Recent single-center studies promote oral penicillin challenges, without skin testing, in patients with low risk/likelihood of true allergy. However, how best to define a low-risk penicillin allergy history is uncertain.

Objective: To statistically determine an optimal low-risk definition, to select patients for safe outpatient penicillin challenges, without skin testing.