Altered CD45 expression in C77G carriers influences immune function and outcome of hepatitis C infection

J Med Genet. 2006 Aug;43(8):678-84. doi: 10.1136/jmg.2005.040485. Epub 2006 Feb 27.

Abstract

Background: A polymorphism in exon 4 (C77G) of CD45 that alters CD45 splicing has been associated with autoimmune and infectious diseases in humans.

Objective: To investigate the effect of C77G in hepatitis C virus (HCV) infected individuals and study the phenotype and function of peripheral blood mononuclear cells (PBMC) from healthy and hepatitis C infected C77G carriers.

Results: C77G individuals showed an increased proportion of primed CD45RA and effector memory CD8 T cells and more rapid activation of the lymphocyte specific protein tyrosine kinase (Lck) following CD3 stimulation. Transgenic mice with CD45 expression mimicking that in human C77G variants had more activated/memory T cells, more rapid proliferative responses, and activation of Lck.

Conclusions: Changes in CD45 isoform expression can alter immune function in human C77G variants and CD45 transgenic mice. The C77G allele may influence the outcome of HCV infection.

Publication types

  • Letter

MeSH terms

  • Animals
  • Biomarkers
  • Carrier State / immunology*
  • Cell Proliferation
  • Exons / genetics
  • Female
  • Flow Cytometry
  • Gene Expression
  • Hepatitis C / genetics*
  • Hepatitis C / immunology*
  • Humans
  • Leukocyte Common Antigens / genetics*
  • Leukocyte Common Antigens / metabolism*
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology

Substances

  • Biomarkers
  • Leukocyte Common Antigens