PXD055246

PXD055246 is an original dataset announced via ProteomeXchange.

Title	DADA2 NETS SHOW DISTINCT PROTEOMIC SIGNATURE FROM POLYARTERITIS NODOSA NETS AND ACTIVATE PRO-INFLAMMATORY CYTOKINES SECRETION FROM DENDRITIC CELLS
Description	Background Adenosine Deaminase 2 Deficiency (DADA2) is an autoinflammatory disease characterized by systemic vasculopathy, strokes and mild immunodeficiency. Recently NETosis has been implicated in the pathogenesis of Deficiency of Adenosine Deaminase 2. Objectives To deep investigate the possible effects of NETs on the immune system we characterized proteomic profile of NETs from DADA2 as compared to HD and Polyarteritis Nodosa (PAN) patients. To determine if NETs contain possibly immunogenic antigens we study functional aspects on Dendritic Cells after in vitro stimulation with NETs. Methods Twenty two DADA2 patients were enrolled. We analyzed NETosis by Imaging Flow Citometry. We evaluated NETs remnants and DNAse in the plasma samples by ELISA assay whereas DNAse activity by DNA digestion. We used quantitative proteomics approach to identify NET proteins in 6 DADA2, 7 PAN and 7 HD. Results Neutrophils from DADA2 patients show a significant increased suicidal NETosis. DNAse enzymes were not normal in the level or activity. By proteomic analysis we identified 1356 proteins among which a hundred of proteins were significantly up or down-modulated in DADA2 NETs as compared to controls NETs in resting condition and after stimulation with PMA, Adenosine and TNFα. DADA2 NETs are significantly more efficient than normal NETs in stimulating patients’ monocyte-derived dendritic cells. Conclusion We identified different pathways significantly upregulated or downregulated in DADA2 NETs versus PAN/HD NETs. This peculiar protein profile could be contribute to activate inflammatory pathways in Dendritic cells in DADA2.
HostingRepository	PRIDE
AnnounceDate	2025-06-23
AnnouncementXML	Submission_2025-06-22_16:13:09.772.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Bartolucci
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-27 06:25:06	ID requested
⏵ 1	2025-06-22 16:13:10	announced

10.1007/s10875-025-01888-w;

Signa S, Bartolucci M, Bonacini M, Bertoni A, Del Zotto G, Corcione A, Petretto A, Della Bella S, Bertelli R, Di Silvestre D, Lomagno A, Mauri P, Caorsi R, Bruschi M, Balin S, Bocca P, Volpi S, Catanoso MG, Cafaro A, Tripodi G, Pellottieri L, Mavilio D, Insalaco A, Croci S, Salvarani C, Gattorno M, Schena F, NET Proteomic Profiling Reveals New Pathways Potentially Implicated in Dendritic Cell-Mediated Inflammation in DADA2 Patients. J Clin Immunol, 45(1):106(2025) [pubmed]

submitter keyword: adenosine deaminase 2, PAN, NETs, NETosis

Andrea Petretto
contact affiliation	IRCCS Istituto G Gaslini
contact email	a.petretto@gmail.com
lab head
Martina Bartolucci
contact affiliation	IRCCS Gaslini
contact email	smartibartolucci@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055246
     1. Label: PRIDE project
     2. Name: DADA2 NETS SHOW DISTINCT PROTEOMIC SIGNATURE FROM POLYARTERITIS NODOSA NETS AND ACTIVATE PRO-INFLAMMATORY CYTOKINES SECRETION FROM DENDRITIC CELLS