LETTER TO JMG

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

R Dawes¹, B Hennig², W Irving³, S Petrova⁴, S Boxall⁴, V Ward⁵, D Wallace⁶, D C Macallan⁷, M Thursz⁸, A Hill⁹, W Bodmer¹⁰, P C L Beverley¹¹, E Z Tchilian¹¹

¹ Edward Jenner Institute for Vaccine Research, Compton, Berkshire, UK
² Wellcome Trust Centre for Human Genetics, Headington, Oxford, UK
³ Division of Microbiology and Infectious Diseases, Queen’s Medical Centre, University of Nottingham, Nottingham, UK
⁴ Edward Jenner Institute for Vaccine Research, Compton
⁵ Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, Cancer Research UK, John Radcliffe Hospital, Oxford
⁶ Edward Jenner Institute for Vaccine Research, Compton
⁷ Centre of Infection, St George’s Hospital, University of London, London SW17, UK
⁸ Hepatology Division, Imperial College Faculty of Medicine, St Mary’s Hospital, London W2, UK
⁹ Wellcome Trust Centre for Human Genetics, Oxford
¹⁰ Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, Oxford
¹¹ Edward Jenner Institute for Vaccine Research, Compton

Correspondence to:
Dr Elma Tchilian
The Edward Jenner Institute for Vaccine Research, Compton, Berkshire RG20 7NN, UK; elma.tchilian{at}jenner.ac.uk

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.

Abbreviations: HCV, hepatitis C virus; HENCORE, Hepatitis C European Network for Cooperative Research; Lck, lymphocyte specific protein tyrosine kinase; PBMC, peripheral blood mononuclear cells; SNP, single nucleotide polymorphism; TcR, T cell receptor

Keywords: CD45; C77G variant; hepatitis C; immune response

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