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

R Dawes; B Hennig; W Irving; S Petrova; S Boxall; V Ward; D Wallace; DC Macallan; M Thursz; A Hill; +3 more... W Bodmer; PCL Beverley; EZ Tchilian; (2006) Altered CD45 expression in C77G carriers influences immune function and outcome of hepatitis C infection. Journal of medical genetics, 43 (8). pp. 678-684. ISSN 0022-2593 DOI: 10.1136/jmg.2005.040485

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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.