Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Chanouzas, Dimitrios and Sagmeister, Michael and Faustini, Sian and Nightingale, Peter and Richter, Alex and Ferro, Charles J and Morgan, Matthew David and Moss, Paul and Harper, Lorraine (2019) Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. The Journal of infectious diseases, 219 (2). pp. 234-244. ISSN 1537-6613.

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Official URL: https://academic.oup.com/jid/article/219/2/234/506...

Abstract

Background

Infection is the leading cause of death in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Expansion of CD4+CD28null T cells is associated with increased risk of infection and mortality, but is only present in cytomegalovirus (CMV)-seropositive individuals. We hypothesized that subclinical CMV reactivation drives CD4+CD28null T-cell expansion, that this is associated with impaired immune response to heterologous antigens, and that antiviral therapy may ameliorate this.

Methods

In a proof-of-concept open-label clinical trial, 38 CMV-seropositive AAV patients were randomized to receive valacyclovir for 6 months or no intervention. CMV reactivation was measured monthly in plasma and urine. CD4+CD28null T cells were enumerated at baseline and at 6 months. At 6 months, 36 patients were vaccinated with a 13-valent pneumococcal vaccine. Serotype-specific immunoglobulin G was assayed before and 4 weeks postvaccination to calculate the antibody response ratio.

Results

Valacyclovir treatment suppressed subclinical CMV reactivation and reduced CD4+CD28null T-cell proportion. CD4+CD28null T-cell reduction correlated with improved vaccine response, whereas CMV reactivation associated with reduced response to vaccination. Furthermore, expansion of CD4+CD28null T cells was associated with a reduction in the functional capacity of the CD4 compartment.

Conclusions

Suppression of CMV may improve the immune response to a T-cell-dependent pneumococcal vaccination in patients with AAV, thus offering potential clinical benefit.

Clinical Trials Registration

NCT01633476.

Item Type: Article
Subjects: QW Microbiology. Immunology
WG Cardiovascular system. Cardiology
WJ Urogenital system. Urology
Divisions: Emergency Services > Renal
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Depositing User: Beth Connors
Date Deposited: 26 Nov 2019 10:05
Last Modified: 26 Nov 2019 10:05
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2616

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