Association Between Cytometric Biomarkers, Clinical Phenotype, and Complications of Common Variable Immunodeficiency

Adam Markocsy; Anna Bobcakova; Otilia Petrovicova; Lenka Kapustova; Eva Malicherova Jurkova; Martina Schniederova; Jela Petriskova; Michal Cibulka; Michaela Hyblova; Milos Jesenak

doi:10.7759/cureus.52941

Association Between Cytometric Biomarkers, Clinical Phenotype, and Complications of Common Variable Immunodeficiency

Cureus. 2024 Jan 25;16(1):e52941. doi: 10.7759/cureus.52941. eCollection 2024 Jan.

Affiliations

¹ Department of Paediatrics, Martin University Hospital, Martin, SVK.
² Department of Pulmonology and Phthisiology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, SVK.
³ Department of Paediatrics, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, SVK.
⁴ Department of Clinical Immunology and Allergology, Martin University Hospital, Martin, SVK.
⁵ Department of Medical Genetics, Medirex a.s., Bratislava, SVK.
⁶ Department of Clinical Immunology and Allergology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, SVK.

Abstract

Background: Common variable immunodeficiency (CVID) is a heterogeneous group of immune disorders. The patients are classified according to the clinical manifestation with the infection-only phenotype (CVID_inf) and CVID with immune dysregulation (CVID_id).

Methods: We performed a retrospective clinical analysis of 64 CVID patients (34 males, 53.13%; mean age: 41.4 years; SD: ±21.4 years). We divided the patients into subgroups according to the clinical manifestation (CVID_inf and CVID_id) and according to B cell phenotypic profiling after performing flow cytometry with the use of the EUROclass classification. We compared clinical manifestations, selected laboratory parameters, and therapy in these groups. All CVID_id patients were tested after the manifestation of complications associated with immune dysregulation and in eight patients during the immunosuppressive treatment (systemic corticosteroids and hydroxychloroquine).

Results: Two-thirds of patients in our cohort had symptoms resulting from immune dysregulation. Almost half of the patients had autoimmune complications. A higher proportion of marginal zone B cells was associated with autoimmune complications. A lower percentage of naïve B cells was connected to autoimmunity, whereas a lower proportion of transitional B cells was associated with rheumatic diseases and splenomegaly. Patients with lymphadenopathy had a higher percentage of double-negative T cells and a lower percentage of switched memory B cells. We performed molecular-genetic testing in 28% (n = 17) of patients and found a causal pathogenic variant in 23.5% (n = 4) of this group.

Conclusion: Based on our results, there is an association between specific cytometric parameters, clinical phenotype, and complications of CVID. The use of the subpopulations of B cells can be helpful in the diagnosis of these specific clinical complications in CVID patients and could help to personalise the therapeutic approach.

Keywords: b cell phenotypic profiling; common variable immunodeficiency; immune dysregulation; marginal zone b cells; transitional b cells.