CVID patients with autoimmunity have elevated T cell expression of granzyme B and HLA-DR and reduced levels of Treg cells

J Clin Pathol. 2013 Feb;66(2):146-50. doi: 10.1136/jclinpath-2012-201046. Epub 2012 Nov 21.

Abstract

Aims: Common variable immunodeficiency (CVID) is a primary antibody immunodeficiency with approximately 20% of patients reporting additional autoimmune symptoms. The primary aim of this study was to compare the levels of activated and regulatory T cells (Treg cells) in CVID patients in an attempt to clarify their possible interactions leading to the generation of autoimmunity.

Methods: Immunophenotyping of T cells was performed by flow cytometry using a whole blood approach. Surface expression of human leukocyte antigen HLA class II DR and intracellular levels of granzyme B in T cell subsets were assessed; Treg levels were measured using CD4 CD25, FOXp3 and CTLA-4.

Results: CVID patients had higher levels of granzyme B and HLA-DR on CD8(+) T cells compared with control values (mean of 59% vs 30% and 45% vs 21%, respectively). Patients also had reduced levels of Treg cells compared with control values (con mean=3.24% vs pat=2.54%). Patients with autoimmunity (5/23) had a similar level of T cell activation markers to the rest of the patients but with lower Treg cells (mean of 1.1%) and reduced CD25 and CTLA-4 expression. Patients with autoimmunity had a higher ratio of activated to Treg cells compared with patients with no autoimmune symptoms.

Conclusions: These results highlight that reduced levels of Treg cells were associated with elevated levels of activated T cells, suggesting that reduced Treg cells in these patients may have functional consequences in allowing exaggerated T cell responses.

MeSH terms

  • Adult
  • Autoimmunity*
  • Biomarkers / analysis
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology
  • CTLA-4 Antigen / analysis
  • Case-Control Studies
  • Common Variable Immunodeficiency / enzymology*
  • Common Variable Immunodeficiency / immunology*
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / analysis
  • Granzymes / analysis*
  • HLA-DR Antigens / analysis*
  • Humans
  • Immunophenotyping / methods
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / enzymology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Up-Regulation

Substances

  • Biomarkers
  • CTLA-4 Antigen
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HLA-DR Antigens
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • GZMB protein, human
  • Granzymes