Interaction between immune cells phenotype and the microbiome in B cells immunodeficiency diseases

: miRNA & microbiomes in PIDDs

Abstract

Background: Deficiency in B-cell development is the most frequent of primary immunodeficiency disorders (PIDD), characterised by complications, making diagnoses and treatment challenging. Patients receive intravenous immunoglobulin (IGIV) and micronutrient supplementation to improve prognosis, with likely changes in biomarkers. Associations were sought between medico-clinical parameters, serum exosomal miRNA and the gut microbiome in patients with PIDD after intravenous immunoglobulin (IGIV) and micronutrient supplementation. Methodology: Ethical approval was granted. Retrospective analysis of data from PIDD (n=48), which included phenotypic classification, inflammatory markers, age at presentation and vitamin D levels, on a subset (n=27). Intervention studies (n=10) of serum exosomal microRNA expression and the gut microbiome were done pre-/post-IGIV and -vitamin (A, E, B, and D) supplementation. Results: Vitamin D deficiency was apparent in patients, compared to reference ranges. Comparisons between patients with PIDD with no complications, as opposed to those with bronchiectasis and/or allergy, showed comparable vitamin D levels (p>0.05). Elevated CRP and lower IgG levels were apparent in patients with bronchiectasis and allergy complication (p<0.05). White blood cell (WBC) counts were higher in patients without complications (p=0.03), perhaps indicating a lower infection rate in this group. Bronchiectasis was higher in patients diagnosed at paediatric age (<14 years; 11 out of 12; 91.7%) compared to adults (9 out of 24; 37.5%) (p=0.002). Smoking was not associated with an increased rate of complications, but males appeared more prone to bronchiectasis (p=0.003). Exosomal miR showed up-regulation in 2 miRNAs (hsa-miR-122-5p and miR-4497) following IGIV and vitamin supplementation. No changes in microbiome diversity were seen. Conclusion: Elevated CRP is a biomarker for B-cell immunodeficiency and bronchiectasis, with miRs, 122-5p and 4497, as mediators of both IGIV and vitamin supplementation. The robustness of CRP and miRs as biomarkers and their role in PIDD need to be confirmed in larger cohorts. Understanding of aetiology of the disease could help design effective therapies and monitoring methods.

Date of Award	28 Nov 2019
Original language	English
Awarding Institution	University of Bristol
Supervisor	David J Morgan (Supervisor) & Wael Kafienah (Supervisor)