PMID- 30375745
OWN - NLM
STAT- MEDLINE
DCOM- 20191227
LR  - 20191227
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 71
IP  - 4
DP  - 2019 Apr
TI  - Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil 
      Cytoplasmic Antibody-Associated Vasculitis.
PG  - 641-650
LID - 10.1002/art.40766 [doi]
AB  - OBJECTIVE: To compare the effects of rituximab (RTX) and conventional 
      immunosuppressants (CIs) on CD4+ T cells, Treg cells, and CD8+ T cells in 
      antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: A 
      thorough immunophenotype analysis of CD4+, Treg, and CD8+ cells from 51 patients 
      with AAV was performed. The production of cytokines and chemokines by CD8+ T 
      cells stimulated in vitro was assessed using a multiplex immunoassay. The impact 
      of AAV B cells on CD8+ T cell response was assessed using autologous and 
      heterologous cocultures. RESULTS: CD4+ and Treg cell subsets were comparable 
      among RTX-treated and CI-treated patients. In contrast, within the CD8+ T cell 
      compartment, RTX, but not CIS, reduced CD45RA+CCR7- (TEMRA) cell frequency (from 
      a median of 39% before RTX treatment to 10% after RTX treatment [P < 0.01]) and 
      efficiently dampened cytokine/chemokine production (e.g., the median macrophage 
      inflammatory protein 1alpha level was 815 pg/ml in patients treated with RTX versus 
      985 pg/ml in patients treated with CIs versus 970 pg/ml in those with active 
      untreated AAV [P < 0.01]). CD8+ T cell subsets cocultured with autologous B cells 
      produced more proinflammatory cytokines in AAV patients than in controls (e.g., 
      for tumor necrosis factor-producing effector memory CD8+ T cells: 14% in AAV 
      patients versus 9.2% in controls [P < 0.05]). In vitro disruption of AAV B 
      cell-CD8+ T cell cross-talk reduced CD8+ T cell cytokine production, mirroring 
      the reduced CD8+ response observed ex vivo after RTX treatment. CONCLUSION: The 
      disruption of a pathogenic B cell/CD8+ T cell axis may contribute to the efficacy 
      of RTX in AAV. Further studies are needed to determine the value of CD8+ T cell 
      immunomonitoring in B cell-targeted therapies.
CI  - (c) 2018, American College of Rheumatology.
FAU - Neel, Antoine
AU  - Neel A
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Bucchia, Marie
AU  - Bucchia M
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Neel, Melanie
AU  - Neel M
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Tilly, Gaelle
AU  - Tilly G
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Caristan, Aurelie
AU  - Caristan A
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Yap, Michele
AU  - Yap M
AD  - CHU Nantes, Nantes, France.
FAU - Rimbert, Marie
AU  - Rimbert M
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Bruneau, Sarah
AU  - Bruneau S
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Cadoux, Marion
AU  - Cadoux M
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Agard, Christian
AU  - Agard C
AD  - CHU Nantes and CIC biotherapie, Nantes, France.
FAU - Hourmant, Maryvonne
AU  - Hourmant M
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes France, and Centre 
      Hospitalier Bretagne Atlantique, Vannes, France.
FAU - Godmer, Pascal
AU  - Godmer P
AD  - Centre Hospitalier Bretagne Atlantique, Vannes, France.
FAU - Brouard, Sophie
AU  - Brouard S
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Bressollette, Celine
AU  - Bressollette C
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Hamidou, Mohamed
AU  - Hamidou M
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Josien, Regis
AU  - Josien R
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Fakhouri, Fadi
AU  - Fakhouri F
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
FAU - Degauque, Nicolas
AU  - Degauque N
AD  - INSERM UMR1064, Universite de Nantes and CHU Nantes, Nantes, France.
LA  - eng
GR  - 602470/European Union's Seventh Framework Programme for Research, Technological 
      Development and Demonstration/International
GR  - ANR-10-IBHU-005/Nantes Metropole and Pays de la Loire Region/International
GR  - ANR-11-LABX-0016-01/Investments for the Future program/International
GR  - ProGreffe Foundation/International
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190308
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Immunosuppressive Agents)
RN  - 4F4X42SYQ6 (Rituximab)
SB  - IM
MH  - Aged
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*drug 
      therapy/*immunology
MH  - B-Lymphocytes/drug effects
MH  - CD4-Positive T-Lymphocytes/drug effects/immunology
MH  - CD8-Positive T-Lymphocytes/*drug effects/immunology
MH  - Female
MH  - Humans
MH  - Immunity, Cellular/drug effects
MH  - Immunophenotyping
MH  - Immunosuppressive Agents/immunology/*pharmacology
MH  - Male
MH  - Middle Aged
MH  - Rituximab/immunology/*pharmacology
MH  - T-Lymphocytes, Regulatory/drug effects/immunology
MH  - Treatment Outcome
EDAT- 2018/10/31 06:00
MHDA- 2019/12/28 06:00
CRDT- 2018/10/31 06:00
PHST- 2018/02/22 00:00 [received]
PHST- 2018/10/25 00:00 [accepted]
PHST- 2018/10/31 06:00 [pubmed]
PHST- 2019/12/28 06:00 [medline]
PHST- 2018/10/31 06:00 [entrez]
AID - 10.1002/art.40766 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2019 Apr;71(4):641-650. doi: 10.1002/art.40766. Epub 2019 
      Mar 8.