A Healthier Wisconsin

Molecular Pathogenesis of Common Variable Immunodeficiency

Studying genetic variants contributing to Common Variable Immunodeficiency to advance the identification of novel target therapeutics

Full Project Name:Molecular Pathogenesis of Common Variable ImmunodeficiencyPrincipal Investigator:Denim Wang, PhD, Microbiology and ImmunologyCo-Investigator:James Verbsky, MD, PhD, Pediatrics; John M Routes, MD, PediatricsAward Amount:$300,000
Award Date
Project Duration:24 months

Project Description Narrative:

Primary immune deficiencies are genetic disorders that result in a poorly functioning immune system. Common Variable Immunodeficiency (CVID) is the most common serious primary immune deficiency disease. A high proportion of these patients manifest with serious autoimmune features which negatively affect their health and survival. Previous studies have found a variety of genetic variants in lymphocyte signaling pathways, but the significance of these genetic variants is unknown. Further study of these genetic variants and the translation of these findings into a model for easier understanding is needed to advance new knowledge and identify treatment or prevention options.

Through this award, investigators aim to provide novel insights into the molecular pathogenesis of human CVID to help identify novel target therapeutics for the disease.

Project Updates:

  • Completed single cell (SC)RNA-seq experiments with PBMCs (peripheral blood mononuclear cells) from Common Variable Immunodeficiency (CVID) patients that identified 10 cell populations for study that correlated with the expected subgroups of T cells
  • Demonstrated that patients with CVID and lung disease had larger populations of memory populations as expected since the patient's immune systems are dysregulated and activated
  • Generated transgenic mice showing B cell impairment, the white blood cells that produce antibodies
  • Completed RNA-seq of B cells, demonstrating impaired B cell activation

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