Synovial membrane protein expression differs between juvenile idiopathic arthritis subtypes in early disease

Abstract

IntroductionJuvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1,000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown. Investigation of disease pathology at the level of the synovial membrane is required if we want to begin to understand the disease at the molecular and biochemical level. The synovial membrane proteome from early disease-stage, treatment naive JIA patients was compared between polyarticular and oligoarticular subgroups.MethodsProtein was extracted from 15 newly diagnosed, treatment naive JIA synovial membrane biopsies and separated by two dimensional fluorescent difference in-gel electrophoresis. Proteins displaying a two-fold or greater change in expression levels between the two subgroups were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry with expression further verified by Western blotting and immunohistochemistry.ResultsAnalysis of variance analysis (P ≤ 0.05) revealed 25 protein spots with a two-fold or greater difference in expression levels between polyarticular and oligoarticular patients. Hierarchical cluster analysis with Pearson ranked correlation revealed two distinctive clusters of proteins. Some of the proteins that were differentially expressed included: integrin alpha 2b (P = 0.04); fibrinogen D fragment (P = 0.005); collagen type VI (P = 0.03); fibrinogen gamma chain (P = 0.05) and peroxiredoxin 2 (P = 0.02). The identified proteins are involved in a number of different processes including platelet activation and the coagulation system.ConclusionsThe data indicate distinct synovial membrane proteome profiles between JIA subgroups at an early stage in the disease process. The identified proteins also provide insight into differentially perturbed pathways which could influence pathological events at the joint level.

Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis

“…Using proteomic analyses and immunoassays, signatures of serum proteins that distinguish two clinical phenotypes of SJIA and help differentiate autoinflammatory SJIA from infections were discovered. Proteomics has been relatively underused in paediatric rheumatology with most studies focusing on synovial fluid protein expression in JIA 32 33. Proteomic analyses have, however, identified serum protein profiles of SJIA and revealed biomarkers for monitoring response to therapy in SJIA 28 34.…”

Wrist Arthroscopy in Juvenile Idiopathic Arthritis: A Review of Current Literature and Future Implications

“…21 A recent study using synovial biopsies identified synovial protein expression patterns that discriminate between clinical subgroups of early JIA. 31 Synovial biopsies are relatively easy to obtain using AS in JIA and may contribute to understanding the early pathological changes and disease process in JIA. 31 Such studies may identify patients who are at high risk of disease progression.…”

“…31 Synovial biopsies are relatively easy to obtain using AS in JIA and may contribute to understanding the early pathological changes and disease process in JIA. 31 Such studies may identify patients who are at high risk of disease progression. Protein modification has been found to be a surrogate marker of uncontrolled inflammation in JIA, and synovial protein analysis could identify patients who are at high risk of disease progression.…”

Psoriatic Arthritis Under a Proteomic Spotlight: Application of Novel Technologies to Advance Diagnosis and Management

“…Quantitative proteomic analysis has been a point of discussion for the past few decades and has been applied in various disease areas to understand the dynamics of the organisms' biological system and its proteomic content [124]. Major advances in the development of label-free DDA and DIA approaches over the last decade have demonstrated to help obtain a vast amount of information and almost a complete sense of the true biological state.…”