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Common Variable Immunodeficiency: More Pathways than Roads to Rome

Xiao P Peng1,2, Andrés Caballero-Oteyza1,3, Bodo Grimbacher1,3,4,5,6

  • 1Institute for Immunodeficiency, Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany;

Annual Review of Pathology
|October 20, 2022
PubMed

Fifty years have elapsed since the term common variable immunodeficiency (CVID) was introduced to accommodate the many and varied antibody deficiencies being identified in patients with suspected inborn errors of immunity (IEIs). Since then, how the term is understood and applied for diagnosis and management has undergone many revisions, though controversy persists on how exactly to define and classify CVID. Many monogenic disorders have been added under its aegis, while investigations into polygenic, epigenetic, and somatic contributions to CVID susceptibility have gained momentum. Expansion of the overall IEI landscape has increasingly revealed genotypic and phenotypic overlap between CVID and various other immunological conditions, while increasingly routine genotyping of CVID patients continues to identify an incredible diversity of pathophysiological mechanisms affecting even single genes. Though many questions remain to be answered, the lessons we have already learned from CVID biology have greatly informed our understanding of adaptive, but also innate, immunity.

Keywords:
B cell developmentgeneticsimmunodeficiencyinborn errors of immunitymutationpathophysiologyprimary antibody deficiencyvariant

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