BACKGROUND: The primary objective of this study was to provide an assessment of NK cells in patients with ANCA-associated vasculitis (AAV). METHODS: Patients were classified based on the presence or absence of ANCAs and compared with healthy controls (HCs). By multiparameter flow cytometry, we evaluated the number and proportion of NK cells (CD3-CD56+) and the CD56dim , CD56bright , CD56dim CD57bright subsets; TLR2 and TLR9 expression; intracellular IFN-γ production upon stimulation with TLR2 and TLR9 ligands; degranulation activity; serum cytokines; immunohistochemical staining of available biopsies. RESULTS: No differences in the number and proportion of NK cells between patients and HC were observed, except for a lower proportion of CD56dim subset in ANCA-negative patients than in HC (P = 0.02). With respect to HC, TLR2 expression levels were reduced in NK cells from ANCA-negative patients (P = 0.03), in the CD56dim subset of ANCA-positive (P = 0.02) and ANCA-negative patients (P = 0.01), in the CD56bright subset of ANCA-positive patients (P = 0.007), and in the CD56dim CD57bright subset of ANCA-positive (P = 0.04) and ANCA-negative patients (P = 0.03). No differences between patients and HC were found concerning IFN-γ production and degranulation activity. IL-22 levels were lower in ANCA-positive patients than in HC (P = 0.01). The immunohistochemical analysis showed sporadic CD56+ cells in one renal biopsy, and a diffuse and moderate infiltrate of IL-22+ cells in all renal biopsies and in skin tissue. CONCLUSIONS: Our data suggest a role of infectious stimuli triggering NK cells in AAV pathogenesis. Poor detection of NK cells in affected tissues suggests a marginal involvement in local inflammatory responses.

Multicolor flow cytometric analysis of TLR2 and TLR9 expression and function in NK cells from patients with ANCA-associated vasculitis / Scrivo, Rossana; Peruzzi, Giovanna; Gattamelata, Angelica; Gross, Catharina C; Carletti, Raffaella; Di Gioia, Cira Rosaria Tiziana; Brandt, Jessica; Priori, Roberta; Morrone, Stefania; Santoni, Angela; Valesini, Guido. - In: CYTOMETRY. PART B, CLINICAL CYTOMETRY. - ISSN 1552-4957. - STAMPA. - 94:3(2018), pp. 412-422. [10.1002/cyto.b.21586]

Multicolor flow cytometric analysis of TLR2 and TLR9 expression and function in NK cells from patients with ANCA-associated vasculitis

SCRIVO, Rossana
Primo
;
PERUZZI, Giovanna
Secondo
;
GATTAMELATA, ANGELICA;CARLETTI, RAFFAELLA;DI GIOIA, Cira Rosaria Tiziana;PRIORI, ROBERTA;MORRONE, Stefania;SANTONI, Angela
Penultimo
;
VALESINI, Guido
Ultimo
2018

Abstract

BACKGROUND: The primary objective of this study was to provide an assessment of NK cells in patients with ANCA-associated vasculitis (AAV). METHODS: Patients were classified based on the presence or absence of ANCAs and compared with healthy controls (HCs). By multiparameter flow cytometry, we evaluated the number and proportion of NK cells (CD3-CD56+) and the CD56dim , CD56bright , CD56dim CD57bright subsets; TLR2 and TLR9 expression; intracellular IFN-γ production upon stimulation with TLR2 and TLR9 ligands; degranulation activity; serum cytokines; immunohistochemical staining of available biopsies. RESULTS: No differences in the number and proportion of NK cells between patients and HC were observed, except for a lower proportion of CD56dim subset in ANCA-negative patients than in HC (P = 0.02). With respect to HC, TLR2 expression levels were reduced in NK cells from ANCA-negative patients (P = 0.03), in the CD56dim subset of ANCA-positive (P = 0.02) and ANCA-negative patients (P = 0.01), in the CD56bright subset of ANCA-positive patients (P = 0.007), and in the CD56dim CD57bright subset of ANCA-positive (P = 0.04) and ANCA-negative patients (P = 0.03). No differences between patients and HC were found concerning IFN-γ production and degranulation activity. IL-22 levels were lower in ANCA-positive patients than in HC (P = 0.01). The immunohistochemical analysis showed sporadic CD56+ cells in one renal biopsy, and a diffuse and moderate infiltrate of IL-22+ cells in all renal biopsies and in skin tissue. CONCLUSIONS: Our data suggest a role of infectious stimuli triggering NK cells in AAV pathogenesis. Poor detection of NK cells in affected tissues suggests a marginal involvement in local inflammatory responses.
File allegati a questo prodotto
File Dimensione Formato  
Scrivo_multicolor-flow-cytometric_2018.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 760.83 kB
Formato Adobe PDF
760.83 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1113962
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact