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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.

Original publication

DOI

10.1136/jmg.2005.040485

Type

Journal article

Journal

J Med Genet

Publication Date

08/2006

Volume

43

Pages

678 - 684

Keywords

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