Plasma protein profiling reflects T H 1-driven immune dysregulation in common variable immunodeficiency

Common variable immunodeficiency (CVID) is a disorder characterized by antibody deficiency. A significant fraction of the patients suffer from immune dysregulation, which leads to increased morbidity and mortality. The pathogenesis of this condition is poorly understood. Our aim was to find out whet...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2020-08, Vol.146 (2), p.417
Main Authors: Hultberg, Jonas, Ernerudh, Jan, Larsson, Marie, Nilsdotter-Augustinsson, Åsa, Nyström, Sofia
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
B-Lymphocytes - pathology
Blood Proteins - metabolism
Cell Proliferation
Chemokine CXCL13 - blood
Common Variable Immunodeficiency - immunology
Female
Flow Cytometry
Humans
Interferon-gamma - metabolism
Interleukin-1beta - metabolism
Lymphocyte Activation
Male
Middle Aged
Proteomics - methods
Signal Transduction
Th1 Cells - pathology
Young Adult
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Summary:Common variable immunodeficiency (CVID) is a disorder characterized by antibody deficiency. A significant fraction of the patients suffer from immune dysregulation, which leads to increased morbidity and mortality. The pathogenesis of this condition is poorly understood. Our aim was to find out whether the plasma protein signature in CVID is associated with clinical characteristics and lymphocyte aberrations. A highly sensitive proximity extension assay was used for targeted profiling of 145 plasma proteins in 29 patients with CVID. Phenotyping of peripheral lymphocytes was done by flow cytometry. The findings were correlated with the burden of immune dysregulation. Unsupervised clustering of plasma protein profiles identified 2 distinct groups of patients with CVID that differed significantly in terms of the degree of complications due to immune dysregulation and in terms of the frequency of activated B- and T-cell subpopulations. Pathway analysis identified IFN-γ and IL-1β as the top enriched upstream regulators associated with higher grade of immune dysregulation. In addition, CVID was found to be associated with increased plasma levels of the B-cell-attracting chemokine CXCL13. Clustering based on plasma protein profiles delineated a subgroup of patients with CVID with activated T cells and clinical complications due to immune dysregulation. Thus, data indicate that CVID-associated immune dysregulation is a T 1-mediated inflammatory process driven by the IFN-γ pathway.
ISSN:1097-6825