Preferential Reduction of Circulating Innate Lymphoid Cells Type 2 in Patients with Common Variable Immunodeficiency with Secondary Complications Is Part of a Broader Immune Dysregulation

J Clin Immunol. 2017 Nov;37(8):759-769. doi: 10.1007/s10875-017-0444-0. Epub 2017 Sep 21.


Purpose: Over a third of patients with common variable immunodeficiency (CVID) suffer from secondary complications like inflammatory organ disease, autoimmune manifestations, or lymphoproliferation contributing to increased morbidity and mortality in affected patients. Innate lymphoid cells (ILCs) have emerging roles in setting the milieu for physiological, but also pathological, immune responses and inflammation. We therefore sought to correlate the recently identified disturbed homeostasis of ILCs with alterations of the adaptive immune system in complex CVID patients (CVIDc).

Methods: We quantified peripheral blood ILC and T helper cell subsets of 58 CVID patients by flow cytometry and compared the results to the clinical and immunological phenotype.

Results: Total ILCs were significantly reduced in peripheral blood of CVIDc patients compared to healthy individuals, but not to CVID patients who suffered only from infections (CVIDio). This reduction was mainly due to a decrease in ILC2s, while ILC3s were relatively increased in CVIDc compared to CVIDio patients. This alteration in ILC phenotype was more prominent in patients with an expansion of CD21low B cells, but we could not detect an association of the altered ILC phenotype with a TH1-shift among circulating CD4 T cells, which was also prominent in CVIDc patients.

Conclusion: We confirm a relative shift in ILCs of CVIDc patients towards ILC3s which was associated with the expansion of CD21low B cells, but not overtly with the relative expansion of TH1-like T cells. Given the relative abundance of TH1-like T cells compared to ILCs, these probably represent a more prominent source of the observed IFNγ-signature in CVIDc patients.

Keywords: CD21low; CD4 T cell; Common variable immunodeficiency (CVID); IFNγ; immune dysregulation; innate lymphoid cells (ILCs).

MeSH terms

  • Adaptive Immunity
  • Adult
  • Aged
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / immunology*
  • Blood Circulation
  • Common Variable Immunodeficiency / complications
  • Common Variable Immunodeficiency / immunology*
  • Cytokines / metabolism
  • Female
  • Homeostasis
  • Humans
  • Immune Tolerance
  • Immunity, Innate*
  • Inflammation
  • Lymphocytes / immunology*
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / immunology*
  • Male
  • Middle Aged
  • Phenotype
  • Th2 Cells / immunology
  • Young Adult


  • Cytokines