Proteomics

Dataset Information

0

PROTEOMIC SIGNATURES OF MONOCYTES IN HEREDITARY RECURRENT FEVERS


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Leukocyte, Blood

DISEASE(S): Autoimmune Disease Of Blood

SUBMITTER: Andrea Petretto  

LAB HEAD: Andrea Petretto

PROVIDER: PXD024068 | Pride | 2022-08-12

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
MQ.zip Other
Penco_Fusion_CAPS_CL_A59_2_096.raw Raw
Penco_Fusion_CAPS_CL_A60_2_097.raw Raw
Penco_Fusion_CAPS_CL_A60_4_098.raw Raw
Penco_Fusion_CAPS_CL_A67_2_099.raw Raw
Items per page:
1 - 5 of 96
altmetric image

Publications


Hereditary periodic recurrent fevers (HRF) are monogenic autoinflammatory associated to mutations of some genes, such as diseases caused by mutations of including MEFV, TNFRSF1A and MVK genes. Despite the identification of the causative genes, the intracellular implications related to each gene variant are still largely unknown. A large -scale proteomic analysis on monocytes of these patients is aimed to identify with an unbiased approach the mean proteins and molecular interaction networks invo  ...[more]

Similar Datasets

2021-12-07 | GSE190181 | GEO
2021-09-08 | PXD014325 | Pride
| PRJNA361002 | ENA
2021-05-10 | GSE161021 | GEO
2011-05-13 | E-GEOD-29267 | biostudies-arrayexpress
2011-07-07 | E-GEOD-30403 | biostudies-arrayexpress
2011-05-13 | GSE29267 | GEO
2011-07-07 | GSE30403 | GEO
2023-01-11 | GSE200690 | GEO
2024-09-08 | GSE252007 | GEO