Clinical Research Directory

Microbiome, Dietary and Quality of Life Analysis of People Living With CVID Treated With or Without Immunoglobulins.

Our research group focusses on finding evidence-based diet strategies to overcome immune dysregulation either due to immune checkpoint inhibitors (ICI) or common variable immunodeficiency (CVID) (Figure 1). CVID is an inborn error of immunity, which is defined, among other factors, by a low level of immunoglobulins, resulting in an increased risk of infections, auto-immune/inflammatory diseases, and cancer. The gut microbiome (GM) plays a crucial role in maintaining immune homeostasis and modulating the host's innate and adaptive immune responses. Modulation of the GM can be achieved by dietary interventions that have been demonstrated to change the composition of the GM within 2 weeks (Oliver et al., 2021). The intake of more than 30 different plant products (vegetables, fruits, seeds and grains) on a weekly basis is associated with a more diverse microbiome in healthy adults (McDonald et al., 2018). Although direct proof of a link between diet and functioning of the immune system is lacking, it is striking that in a retrospective study, melanoma patients treated with immune checkpoint inhibitors (ICI) had a better overall survival when they consumed enough fibers without taking probiotics (Spencer et al., 2021). Currently, we have included 54 of 60 foreseen patients receiving ICI in an interventional study (FORX-01 (NCT05832606)) at our centre, providing them weekly with 30 different plants to be integrated in their diet (funded by Delhaize and FWO). The aim is to measure if the interventional group develops less immune-related adverse events (= side effects of ICI) by changing their GM. Similarly, we hypothesize that introducing a fiber-rich diet in patients with CVID will result in a more diverse GM leading to a decrease in autoimmune disorders and infections and as such lead to an improvement of quality of life. To challenge this hypothesis, we plan to organize a similar diet trial, called KNIVES. To prepare this study, we will first perform an observational study to describe the microbiome of people with CVID (DELICIOUS) followed at UZ Brussel.

Systematic Search for Primary Immunodeficiency in Adults With Infections

Antibody deficiencies and complement deficiencies are the most frequent Primary immunodeficiencies (PIDs) in adults, and are associated with greatly increased susceptibility to recurrent and/or severe bacterial infections - especially upper and lower respiratory tract infections and meningitis. The literature data suggest that PIDs are under-diagnosed in adults. The current European and US guidelines advocate screening adults for PIDs if they present recurrent benign especially upper and lower respiratory tract infections, or if they have experienced at least two severe bacterial infections and/or have a recurrent need for intravenous antibiotics. The objective of the demonstrate the interest of PIDs screening in adult patients who present such recurrent infections and/or after the first severe bacterial infection, especially when the patients do not present with known, etiologically relevant comorbidities.

Genetic Variation in IgG in Alpha 1 Antitrypsin Deficiency

The goal of this study is to learn whether patients who have a genetic mutation in the genes that cause alpha 1 antitrypsin deficiency also have genetic variation in nearby genes that can increase risk for reduced immune function and respiratory infections. To investigate this hypothesis, we will compare immune responses to the 20-valent pneumococcal conjugate vaccine (PCV20, Pfizer) between participants who have one abnormal copy of the SERPINA1 gene and either no COPD exacerbations, vs those with 2 or more COPD exacerbations in the past year.