Expression of IL-17RA in Innate Cells of Patients with Common Variable Immunodeficiency (CVID) and its Clinical Implications
Pedro Botelho Alves
pedrobvalves@gmail.com1, Helena Pires Pereira
1, Jóni Costa Carvalho
1, Inês Nunes
1, Ana Todo-Bom
1,2, Emília Faria
1,*, Frederico Regateiro
1,2,3,*, Artur Paiva
4,*Show more: Authors information and Publication history1Allergy and Clinical Immunology Unit, Coimbra Hospital and University Centre (CHUC), Coimbra, Portugal
2Institute of Immunology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
3Center for Innovative Biomedicine and Biotechnology (CIBB), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
4Flow Cytometry - Pathology Unit, University of Coimbra, Coimbra, Portugal
*Contributed equally
HistoryPublished: 23 January 2024
Accepted: 22 January 2024
Received: 10 October 2023
Doi10.23822/EurAnnACI.1764-1489.326SummaryBackground. Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by B-cell dysfunction and immunoglobulin production deficiency. Dysregulation of interleukin-17 (IL-17) and its receptor IL-17RA have been reported in various immune disorders. This study aimed to investigate the expression of IL-17RA in innate immune cells of CVID patients and its correlation with clinical manifestations.
Methods. A cross-sectional study included 22 CVID patients and 14 age- and sex-matched healthy controls. IL-17RA expression was assessed in various immune cell subsets using flow cytometry. Demographic and clinical data were collected, and statistical analysis was performed.
Results. CVID patients had elevated IL-17RA expression in neutrophils, non-classical monocytes, and dendritic cells compared to healthy controls. Patients with a history of intestinal microbial colonization, particularly with Campylobacter jejuni and Giardia intestinalis, showed significantly higher IL-17RA expression in innate cells. Elevated IL-17RA expression in monocytes and dendritic cells also correlated with higher fecal calprotectin levels in CVID patients, regardless of microbial colonization.
Conclusions. The study suggests that despite previous reports of reduced circulating Th17 cells and IL-17 levels in CVID patients, IL-17RA expression in innate cells may be elevated, potentially indicating altered IL-17 signaling. This heightened IL-17RA expression could contribute to a persistent pro-inflammatory state, possibly due to microbial translocation or other inflammatory factors. The association of IL-17RA expression with gastrointestinal microbial colonization and its correlation with fecal calprotectin underscores the complexity of IL-17RA's role in CVID pathophysiology. Further research in larger cohorts could elucidate the implications of IL-17RA expression in both infectious and non-infectious inflammatory aspects of CVID.
Key wordsCVID; primary immunodeficiency; interleukin-17; inflammation; innate immunity.
FULL TEXT