PMID- 35438139
OWN - NLM
STAT- MEDLINE
DCOM- 20221227
LR  - 20230223
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
VI  - 62
IP  - 1
DP  - 2022 Dec 23
TI  - Cytokine profile, ferritin and multi-visceral involvement characterize macrophage 
      activation syndrome during adult-onset Still's disease.
PG  - 321-329
LID - 10.1093/rheumatology/keac247 [doi]
AB  - OBJECTIVES: To multidimensionally characterize macrophage activation syndrome 
      (MAS) complicating adult-onset Still's disease (AOSD) considering cytokine 
      profile, inflammatory markers and multi-visceral involvement of the disease. To 
      perform a high-dimensional phenotypic analysis of circulating immune cells in 
      AOSD patients with and without MAS. To assess interferon (IFN)-related pathways 
      in AOSD synovial tissues by a bulky RNA sequencing. METHODS: Clinical and 
      biologic data were collected and compared in AOSD patients with and without MAS. 
      Sera biomolecules were analysed by Luminex multiplexing technology. Mass 
      cytometry (CyTOF) was used to characterize circulating immune cells. A bulky RNA 
      sequencing was performed in AOSD synovial tissues. RESULTS: Forty consecutive 
      AOSD patients were assessed, 14 complicated with MAS. Paralleling with increases 
      of systemic score and ferritin, MAS patients showed higher levels of IL-1alpha, 
      IL-1beta, IL-1Ra, IL-2Ra, IL-6, IL-10, IL-17A, IFN-gamma, G-CSF, MCP-1, MIP-1alpha and SCF. 
      Combining the discriminatory ability of these data in identifying MAS, the best 
      model was composed by systemic score, ferritin, IFN-gamma and IL-10. By CyTOF 
      analysis, MAS patients showed an increase of circulating 'classical monocytes' 
      and a reduction of total NK cells. Our assessment showed 3477 IFN-related genes 
      (IRGs) were differently expressed in AOSD synovial tissues. CONCLUSIONS: A 
      multidimensional characterization of AOSD patients suggested that IFN-gamma, IL-10, 
      ferritin and systemic score discriminated the occurrence of cytokine storm 
      syndrome associated with MAS. The inflammatory milieu of AOSD and MAS may be 
      related to a signature of circulating immune cells. Finally, our results about 
      IRGs reinforced the role of IFN-gamma in these patients.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology. All rights reserved. For permissions, please 
      email: journals.permissions@oup.com.
FAU - Ruscitti, Piero
AU  - Ruscitti P
AD  - Department of Biotechnological and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila.
FAU - Ursini, Francesco
AU  - Ursini F
AUID- ORCID: 0000-0001-8194-8642
AD  - Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli.
AD  - Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University 
      of Bologna, Bologna.
FAU - Berardicurti, Onorina
AU  - Berardicurti O
AUID- ORCID: 0000-0002-2808-1581
AD  - Department of Biotechnological and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila.
FAU - Masedu, Francesco
AU  - Masedu F
AD  - Department of Biotechnological and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila.
AD  - Academy of Sciences of Abruzzo Region, Abruzzo.
FAU - Bozzalla Cassione, Emanuele
AU  - Bozzalla Cassione E
AUID- ORCID: 0000-0001-6578-6938
AD  - Rheumatology Department, Fondazione IRCCS Policlinico San Matteo, University of 
      Pavia, Pavia.
FAU - Naldi, Susanna
AU  - Naldi S
AD  - Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli.
AD  - Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University 
      of Bologna, Bologna.
FAU - Di Cola, Ilenia
AU  - Di Cola I
AD  - Department of Biotechnological and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila.
FAU - Di Muzio, Claudia
AU  - Di Muzio C
AD  - Department of Biotechnological and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila.
FAU - De Stefano, Ludovico
AU  - De Stefano L
AD  - Rheumatology Department, Fondazione IRCCS Policlinico San Matteo, University of 
      Pavia, Pavia.
FAU - Di Nino, Elena
AU  - Di Nino E
AD  - Department of Biotechnological and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila.
FAU - Navarini, Luca
AU  - Navarini L
AD  - Rheumatology and Immunology Unit, Department of Medicine, University of Rome 
      Campus Biomedico, Rome.
FAU - Vomero, Marta
AU  - Vomero M
AD  - Rheumatology and Immunology Unit, Department of Medicine, University of Rome 
      Campus Biomedico, Rome.
FAU - Bugatti, Serena
AU  - Bugatti S
AD  - Rheumatology Department, Fondazione IRCCS Policlinico San Matteo, University of 
      Pavia, Pavia.
FAU - Valenti, Marco
AU  - Valenti M
AD  - Department of Biotechnological and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila.
FAU - Mariani, Erminia
AU  - Mariani E
AD  - Department of Medical and Surgical Sciences, Alma Mater Studiorum University of 
      Bologna.
AD  - Laboratory of Immunorheumatology and Tissue Regeneration, Istituto di Ricovero e 
      Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli, Bologna.
FAU - Iagnocco, Annamaria
AU  - Iagnocco A
AD  - Academic Rheumatology Centre, Ospedale Mauriziano - Dipartimento Scienze Cliniche 
      e Biologiche, Universita degli Studi di Torino, Turin, Italy.
FAU - Montecucco, Carlomaurizio
AU  - Montecucco C
AD  - Rheumatology Department, Fondazione IRCCS Policlinico San Matteo, University of 
      Pavia, Pavia.
FAU - Giacomelli, Roberto
AU  - Giacomelli R
AD  - Rheumatology and Immunology Unit, Department of Medicine, University of Rome 
      Campus Biomedico, Rome.
FAU - Cipriani, Paola
AU  - Cipriani P
AD  - Department of Biotechnological and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 130068-27-8 (Interleukin-10)
RN  - 9007-73-2 (Ferritins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Still's Disease, Adult-Onset
MH  - Interleukin-10
MH  - *Macrophage Activation Syndrome/complications
MH  - Ferritins
MH  - Interferon-gamma
OTO - NOTNLM
OT  - adult-onset Still's disease
OT  - cytokine storm syndrome
OT  - macrophage activation syndrome
EDAT- 2022/04/20 06:00
MHDA- 2022/12/28 06:00
CRDT- 2022/04/19 08:40
PHST- 2022/03/07 00:00 [received]
PHST- 2022/04/01 00:00 [revised]
PHST- 2022/04/20 06:00 [pubmed]
PHST- 2022/12/28 06:00 [medline]
PHST- 2022/04/19 08:40 [entrez]
AID - 6570582 [pii]
AID - 10.1093/rheumatology/keac247 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2022 Dec 23;62(1):321-329. doi: 
      10.1093/rheumatology/keac247.