PXD024068

PXD024068 is an original dataset announced via ProteomeXchange.

Title	PROTEOMIC SIGNATURES OF MONOCYTES IN HEREDITARY RECURRENT FEVERS
Description	Hereditary recurrent fevers (HRF) are a group of monogenic autoinflammatory diseases characterized by auto-resolving attacks of sterile inflammation caused by mutations of MEFV, TNFRSF1A and MVK genes1-3. Familial Mediterranean fever (FMF) is the prototype of a HPR and is caused by gain-of-function mutations of the MEFV gene, coding for pyrin4 5. Pyrin is part of the Pyrin-Inflammasome that controls the activation and secretion of interleukin (IL)-1β and can be activated by the cortical actin cytoskeleton remodeling induced by bacterial toxins via RhoA. Mevalonate kinase deficiency (MKD) is secondary to bi-allelic mutations of the gene coding for mevalonate kinase (MVK), an enzyme involved in the cholesterol biosynthesis. Loss-of-function MVK mutations lead to a defective sterol synthesis and to a reduced prenylation of small G proteins, such as RhoA, favoring the activation of the Pyrin-inflammasome6-8. TNF receptor-associated periodic syndrome (TRAPS) is secondary to autosomal dominant mutations of the gene coding for the type I receptor for TNF (TNFRSF1A), resulting in a heap of misfolded TNF receptor 1 in the endoplasmic reticulum, leading to oxidative stress, defective autophagy and consequent over-secretion of pro-inflammatory cytokines9 10. The clinical manifestations of HRFs are rather unspecific and consist mainly in fever, serositis, skin rash, limb and articular pain. No specific biomarkers able to distinguish one among the different HRFs have been identified, so far11. Moreover, the majority of the studies investigating the pathogenic consequences of the genes’ mutations associated with the three HRFs were focused on the few mechanisms classically associated to the pro-inflammatory activation of cells of the innate immunity (NF-kB and MAPK activation, IL-1b activation and secretion). Conversely, an unbiased analysis of possible additional intracellular pathways involved in the different conditions has not been exploited. Recently, large-scale proteomics based on high-resolution mass spectrometry (MS) has offered a systems-wide hypothesis-free method to analyze intracellular pathways in order to identify new disease biomarkers12-14. Here, we analyzed the proteomic signature of unstimulated and stimulated monocytes of patients with FMF, TRAPS and MKD, describing the dysregulated intracellular pathways associated with each condition for the identification of possible biomarkers and possible novel therapeutic targets.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-12_03:35:28.778.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrea Petretto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-08 09:29:22	ID requested
⏵ 1	2022-08-12 03:35:29	announced

Penco F, Petretto A, Lavarello C, Papa R, Bertoni A, Omenetti A, Gueli I, Finetti M, Caorsi R, Volpi S, Gattorno M, Proteomic Signatures of Monocytes in Hereditary Recurrent Fevers. Front Immunol, 13():921253(2022) [pubmed]

submitter keyword: FMF, TRAPS, MKD

Andrea Petretto
contact affiliation	IRCCS IST. G. Gaslini
contact email	a.petretto@gmail.com
lab head
Andrea Petretto
contact affiliation	Gaslini Children's Hospital
contact email	a.petretto@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024068
     1. Label: PRIDE project
     2. Name: PROTEOMIC SIGNATURES OF MONOCYTES IN HEREDITARY RECURRENT FEVERS