Persistent deficiency of circulating mucosal-associated invariant T (MAIT) cells in ANCA-associated vasculitis.
Mucosal associated invariant T cells (MAIT) and innate lymphoid cells (ILCs) have immunoregulatory functions at mucosal sites and have been involved in various inflammatory and autoimmune diseases. The aim of this study was to assess their frequencies in blood in ANCA-associated vasculitis (AAV).



The frequencies and function of MAIT cells, ILCs, γδT, iNKT, NK cells were analyzed by flow cytometry on PBMC of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) without any treatment, in acute (AP) and remission phase (RP) and compared with healthy controls (HC).



The frequencies of MAIT cells were strongly decreased in GPA and MPA in AP compared to HC, both in never treated and in relapsing patients and independently of patient age. This was associated with an activated phenotype of patient MAIT cells, as shown by increased expression of CD69 and IFNγ. MAIT cells remained decreased during RP in AAV patients. The frequencies of iNKT and γδT cells were unaffected compared to HC, whereas those of NK cells were slightly reduced during AP in MPA. We also observed a significant decrease in frequencies of total ILCs with decreased ILC2 and ILC3 and increased ILC1 during AP in both GPA and MPA compared to HC. These frequencies normalized during RP. Interestingly, we observed a significant correlation between the frequency of total ILCs and BVAS.



We show for the first time that AAV are associated with a major decrease and an activated phenotype of blood MAIT cell. These features persisted during remission suggesting a role for MAIT cells in the pathogenesis of AAV.
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France.
Cécile
C
Braudeau
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, F-44000, France.
Karine
K
Amouriaux
INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; CHU Nantes, Service de Médecine Interne, Nantes, F-44000, France.
Antoine
A
Néel
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France.
Guillaume
G
Herbreteau
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, F-44000, France.
Nina
N
Salabert
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France.
Marie
M
Rimbert
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; Université de Nantes, Faculté de Médecine, Nantes, F-44000, France.
Jérôme C
JC
Martin
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France.
Caroline
C
Hémont
INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, Faculté de Médecine, Nantes, F-44000, France; CHU Nantes, Service de Médecine Interne, Nantes, F-44000, France.
Mohamed
M
Hamidou
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, F-44000, France; Université de Nantes, Faculté de Médecine, Nantes, F-44000, France. Electronic address: Regis.josien@univ-nantes.fr.
Régis
R
Josien
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines
ANCA; ANCA-Associated vasculitis; Innate immunity; Innate lymphoid cells; MAIT cells