Proteomic aptamer analysis reveals serum biomarkers associated with disease mechanisms and phenotypes of systemic sclerosis

Frontiers in Immunology

Immunology

Stefano Rodolfi¹  Maria De Santis¹  Angela Ceribelli¹  Francesca Motta¹  Giovanni Costanzo¹  Antonio Tonutti¹  Carlo Selmi¹  Natasa Isailovic² 

[1] Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy;Rheumatology and Clinical Immunology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Italy;Rheumatology and Clinical Immunology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Italy;

关键词: connective tissue disease;    interstitial lung disease;    proteomics;    aptamer technology;    immunology;   

DOI  :  10.3389/fimmu.2023.1246777

 received in 2023-06-24, accepted in 2023-08-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundSystemic sclerosis (SSc) is an autoimmune connective tissue disease that affects multiple organs, leading to elevated morbidity and mortality with limited treatment options. The early detection of organ involvement is challenging as there is currently no serum marker available to predict the progression of SSc. The aptamer technology proteomic analysis holds the potential to correlate SSc manifestations with serum proteins up to femtomolar concentrations.MethodsThis is a two-tier study of serum samples from women with SSc (including patients with interstitial lung disease - ILD - at high-resolution CT scan) and age-matched healthy controls (HC) that were first analyzed with aptamer-based proteomic analysis for over 1300 proteins. Proposed associated proteins were validated by ELISA first in an independent cohort of patients with SSc and HC, and selected proteins subject to further validation in two additional cohorts.ResultsThe preliminary aptamer-based proteomic analysis identified 33 proteins with significantly different concentrations in SSc compared to HC sera and 9 associated with SSc-ILD, including proteins involved in extracellular matrix formation and cell-cell adhesion, angiogenesis, leukocyte recruitment, activation, and signaling. Further validations in independent cohorts ultimately confirmed the association of specific proteins with early SSc onset, specific organ involvement, and serum autoantibodies.ConclusionsOur multi-tier proteomic analysis identified serum proteins discriminating patients with SSc and HC or associated with different SSc subsets, disease duration, and manifestations, including ILD, skin involvement, esophageal disease, and autoantibodies.

【 授权许可】

Unknown   
Copyright © 2023 Motta, Tonutti, Isailovic, Ceribelli, Costanzo, Rodolfi, Selmi and De Santis