PMID- 30102389
OWN - NLM
STAT- MEDLINE
DCOM- 20191118
LR  - 20240313
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 219
IP  - 2
DP  - 2019 Jan 7
TI  - Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion 
      and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil 
      Cytoplasmic Antibody-Associated Vasculitis.
PG  - 234-244
LID - 10.1093/infdis/jiy493 [doi]
AB  - 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.
FAU - Chanouzas, Dimitrios
AU  - Chanouzas D
AD  - Institute of Inflammation and Ageing, College of Medical and Dental Sciences, 
      University of Birmingham, United Kingdom.
AD  - Department of Nephrology, University Hospitals Birmingham National Health Service 
      Foundation Trust, United Kingdom.
FAU - Sagmeister, Michael
AU  - Sagmeister M
AD  - Institute of Inflammation and Ageing, College of Medical and Dental Sciences, 
      University of Birmingham, United Kingdom.
AD  - Department of Nephrology, University Hospitals Birmingham National Health Service 
      Foundation Trust, United Kingdom.
FAU - Faustini, Sian
AU  - Faustini S
AD  - Institute of Immunology and Immunotherapy, College of Medical and Dental 
      Sciences, University of Birmingham, United Kingdom.
FAU - Nightingale, Peter
AU  - Nightingale P
AD  - Institute of Translational Medicine Birmingham, United Kingdom.
FAU - Richter, Alex
AU  - Richter A
AD  - Institute of Immunology and Immunotherapy, College of Medical and Dental 
      Sciences, University of Birmingham, United Kingdom.
FAU - Ferro, Charles J
AU  - Ferro CJ
AD  - Department of Nephrology, University Hospitals Birmingham National Health Service 
      Foundation Trust, United Kingdom.
AD  - Institute of Translational Medicine Birmingham, United Kingdom.
FAU - Morgan, Matthew David
AU  - Morgan MD
AD  - Department of Nephrology, University Hospitals Birmingham National Health Service 
      Foundation Trust, United Kingdom.
AD  - Institute of Clinical Sciences, College of Medical and Dental Sciences, 
      University of Birmingham, United Kingdom.
FAU - Moss, Paul
AU  - Moss P
AD  - Institute of Immunology and Immunotherapy, College of Medical and Dental 
      Sciences, University of Birmingham, United Kingdom.
FAU - Harper, Lorraine
AU  - Harper L
AD  - Department of Nephrology, University Hospitals Birmingham National Health Service 
      Foundation Trust, United Kingdom.
AD  - Institute of Translational Medicine Birmingham, United Kingdom.
AD  - Institute of Clinical Sciences, College of Medical and Dental Sciences, 
      University of Birmingham, United Kingdom.
LA  - eng
SI  - ClinicalTrials.gov/NCT01633476
GR  - MR/R011230/1/MRC_/Medical Research Council/United Kingdom
GR  - 097962/Z/11/Z/WT_/Wellcome Trust/United Kingdom
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antiviral Agents)
RN  - 0 (CD28 Antigens)
RN  - 0 (Pneumococcal Vaccines)
RN  - MZ1IW7Q79D (Valacyclovir)
SB  - IM
MH  - Aged
MH  - Antibodies, Antineutrophil Cytoplasmic/*immunology
MH  - Antibodies, Viral/therapeutic use
MH  - Antiviral Agents
MH  - CD28 Antigens/*immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cytomegalovirus/*immunology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pneumococcal Infections/immunology
MH  - Pneumococcal Vaccines/*immunology
MH  - Vaccination
MH  - Valacyclovir
MH  - Vasculitis/*immunology
MH  - Viral Load
PMC - PMC6306020
EDAT- 2018/08/14 06:00
MHDA- 2019/11/19 06:00
PMCR- 2018/08/09
CRDT- 2018/08/14 06:00
PHST- 2018/05/15 00:00 [received]
PHST- 2018/08/08 00:00 [accepted]
PHST- 2018/08/14 06:00 [pubmed]
PHST- 2019/11/19 06:00 [medline]
PHST- 2018/08/14 06:00 [entrez]
PHST- 2018/08/09 00:00 [pmc-release]
AID - 5068409 [pii]
AID - jiy493 [pii]
AID - 10.1093/infdis/jiy493 [doi]
PST - ppublish
SO  - J Infect Dis. 2019 Jan 7;219(2):234-244. doi: 10.1093/infdis/jiy493.