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Antibody response on polysaccharide- and protein-based vaccines is useful to test B cell functionality. As only few studies have explored the value of studying immune response to both vaccines, we evaluated the clinical value of anti-polysaccharide and anti-protein Luminex-based multiplex assays in context of primary immunodeficiency (PID) diagnosis. A 10-plex Luminex-based assay detecting antibodies to ten pneumococcal polysaccharide (PnPS) serotypes [present in unconjugated Pneumovax, not in 13-valent pneumococcal conjugated vaccine (PCV)] and a 5-plex assay detecting antibodies to five protein antigens (present in DTap/Tdap) were clinically validated in healthy individuals (n=99) and in retrospective (n=399) and prospective (n=108) patient cohorts. Clinical features of individuals with impaired response to PnPS and/or proteins were compared to those with normal response. Antigen-specific antibody thresholds were determined in healthy individuals. Individuals with impaired anti-PnPS responses and deficient immunoglobulin levels suffered more from autoimmune diseases and had lower B cell levels compared to individuals with impaired anti-PnPS response with normal immunoglobulin levels. Individuals with combined impaired response to PnPS and proteins showed more severe clinical manifestations compared to individuals with isolated impaired response to PnPS or proteins. Eight of the 11 individuals with severely impaired responses to both PnPS and proteins had common variable immunodeficiency. Evaluation of the anti-PnPS response to four serotypes not contained in 20-valent PCV was comparable to evaluation to ten serotypes not contained in 13-valent PCV. Multiplexed assessment of anti-PnPS and anti-protein responses combined with immunoglobulin quantification provides useful clinical information to support PID diagnosis. [ABSTRACT FROM AUTHOR]

Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and life-threatening infections most commonly occur in the first years of life. In adults, elderly and immunocompromised people are most vulnerable. Recently there has been an acceleration in the development of candidate RSV vaccines, monoclonal antibodies and therapeutics which are expected to become available in Europe within the next 2–10 years. Understanding the true burden of childhood RSV disease will become very important to support public health authorities and policy makers in the assessment of new therapeutic opportunities against RSV disease. A systematic literature search was performed to map local data on the burden of RSV disease and to evaluate available RSV surveillance systems. A group of 9 paediatric infectious diseases specialists participated in an expert panel. The purpose of this meeting was to evaluate and map the burden associated with RSV infection in children, including patient pathways and the epidemiological patterns of virus circulation in Belgium. Sources of information on the burden of RSV disease in Belgium are very limited. For the outpatient setting, it is estimated that 5–10% of young patients seen in primary care are referred to the hospital. Around 3500 children between 0 and 12 months of age are hospitalized for RSV-bronchiolitis every year and represent the majority of all hospitalizations. The current Belgian RSV surveillance system was evaluated and found to be insufficient. Knowledge gaps are highlighted and future perspectives and priorities offered. Conclusion: The Belgian population-based RSV surveillance should be improved, and a hospital-led reporting system should be put in place to enable the evaluation of the true burden of RSV disease in Belgium and to improve disease management in the future. What is Known: • RSV bronchiolitis is a very important cause of infant hospitalization. • The burden of disease in the community is poorly studied and underestimated. What is New: • This expert opinion summarizes knowledge gaps and offers insights that allow improvement of local surveillance systems in order to establish a future-proof RSV surveillance system. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a life-shortening genetic disease, affecting multiple life domains including physical activity (PA). Although higher PA levels are associated with multiple health benefits, little insight exists on the PA level of people with CF (PwCF) compared to healthy peers. Evidence on the influencing factors (i.e. correlates) of PA in this clinical population is scarce, but essential to fully understand their PA behaviour. Therefore, the present review aims to provide an overview of the PA level of PwCF compared to healthy peers, and the correlates of PA in PwCF. A systematic search of three databases resulted in 46 included studies. Analysis of 16 studies showed that the CF population is equally active compared to healthy peers, but there is a trend towards less high-intensity PA in youths with CF. Furthermore, PA is positively associated with quality of life, lung function, (maximal) exercise capacity, bone mineral density and quadriceps force. Also, PA was lower on weekdays compared to weekend days and lower when experiencing pulmonary exacerbations. More high-quality research is required in PwCF, particularly longitudinal studies that further explore the correlates of PA, with PA investigated as a primary outcome and measured objectively. [ABSTRACT FROM AUTHOR]

Background: Serotype-specific antibody responses to unconjugated pneumococcal polysaccharide vaccine (PPV) evaluated by a World Health Organization (WHO)-standardized enzyme-linked immunosorbent assay (ELISA) are the gold standard for diagnosis of specific polysaccharide antibody deficiency (SAD). The American Academy of Allergy, Asthma and Immunology (AAAAI) has proposed guidelines to interpret the PPV response measured by ELISA, but these are based on limited evidence. Additionally, ELISA is costly and labor-intensive. Measurement of antibody response to Salmonella typhi (S. typhi) Vi vaccine and serum allohemagglutinins (AHA) have been suggested as alternatives. However, there are no large cohort studies and cutoff values are lacking. Objective: To establish cutoff values for antipneumococcal polysaccharide antibody response, anti-S. typhi Vi antibody and AHA. Methods: One hundred healthy subjects (10-55 years) were vaccinated with PPV and S. typhi Vi vaccine. Blood samples were obtained prior to and 3-4 weeks after vaccination. Polysaccharide responses to 3 serotypes were measured by WHO ELISA and to 12 serotypes by an in-house bead-based multiplex assay. Anti-S. typhi Vi IgG were measured with a commercial ELISA kit. AHA were measured by agglutination method. results: Applying AAAAI criteria, 30% of healthy subjects had a SAD. Using serotype-specific fifth percentile (p5) cutoff values for postvaccination IgG and fold increase pre-over postvaccination, only 4% of subjects had SAD. One-sided 95% prediction intervals for anti-S. typhi Vi postvaccination IgG (⩾11.2 U/ml) and fold increase (⩾2) were established. Eight percent had a response to S. typhi Vi vaccine below these cutoffs. AHA titer p5 cutoffs were 1/2 for anti-B and 1/4 for anti-A. Conclusion: We establish reference cutoff for interpretation of PPV responce measured by bead-based assay, cutoff values for S. Typhi vi vaccince responses and normal values for AHA. For the first time, the intraindividual consistency of all three method is studied in a large cohort. [ABSTRACT FROM AUTHOR]

Background: Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome. Methods: Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome. Results: The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood. Conclusions: These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients. [ABSTRACT FROM AUTHOR]

Vitamin A intoxication is a rare cause of liver disease, but the risk increases in patients with underlying liver dysfunction. We present a patient with Shwachman-Diamond Syndrome who developed liver fibrosis, portal hypertension and very severe hepatopulmonary syndrome as a consequence of chronic vitamin A intoxication. She underwent successful liver transplantation with complete resolution of the pulmonary shunting. [ABSTRACT FROM AUTHOR]