Jonas Hultberg1, Jan Ernerudh2, Marie Larsson3, Åsa Nilsdotter-Augustinsson4, Sofia Nyström5. 1. Division of Molecular Virology, Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Clinical Immunology and Transfusions Medicine, and Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden. 2. Department of Clinical Immunology and Transfusions Medicine, and Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden. 3. Division of Molecular Virology, Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden. 4. Department of Infectious Diseases, and Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden. 5. Division of Molecular Virology, Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Clinical Immunology and Transfusions Medicine, and Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden. Electronic address: sofia.c.nystrom@liu.se.
Abstract
BACKGROUND: 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. OBJECTIVE: Our aim was to find out whether the plasma protein signature in CVID is associated with clinical characteristics and lymphocyte aberrations. METHODS: 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. RESULTS: 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. CONCLUSION: 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 TH1-mediated inflammatory process driven by the IFN-γ pathway.
BACKGROUND: 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. OBJECTIVE: Our aim was to find out whether the plasma protein signature in CVID is associated with clinical characteristics and lymphocyte aberrations. METHODS: 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. RESULTS: 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. CONCLUSION: 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 TH1-mediated inflammatory process driven by the IFN-γ pathway.
Authors: Per Wågström; Åsa Nilsdotter-Augustinsson; Mats Nilsson; Janne Björkander; Charlotte Dahle; Sofia Nyström Journal: Front Immunol Date: 2022-01-10 Impact factor: 7.561
Authors: Miranda L Abyazi; Kayla A Bell; Gavin Gyimesi; Turner S Baker; Minji Byun; Huaibin M Ko; Charlotte Cunningham-Rundles; Feng Feng; Paul J Maglione Journal: J Allergy Clin Immunol Date: 2021-06-17 Impact factor: 10.793
Authors: Roos-Marijn Berbers; Julia Drylewicz; Pauline M Ellerbroek; Joris M van Montfrans; Virgil A S H Dalm; P Martin van Hagen; Baerbel Keller; Klaus Warnatz; Annick van de Ven; Jaap M van Laar; Stefan Nierkens; Helen L Leavis Journal: J Clin Immunol Date: 2020-11-15 Impact factor: 8.317