New Proteins Contributing to Immune Cell Infiltration and Pannus Formation of Synovial Membrane from Arthritis Diseases.

Dominique De Seny,Elettra Bianchi,Dominique Baiwir,Gaël Cobraiville,Gabriel Mazzucchelli,Marie-Joëlle Kaiser,Céline Deroyer,Christophe Poulet,Jean-Philippe Hauzeur,Michel Malaise,Olivier Malaise,Geneviève Paulissen,Philippe Delvenne

doi:10.3390/ijms23010434

Abstract

An inflamed synovial membrane plays a major role in joint destruction and is characterized by immune cells infiltration and fibroblast proliferation. This proteomic study considers the inflammatory process at the molecular level by analyzing synovial biopsies presenting a histological inflammatory continuum throughout different arthritis joint diseases. Knee synovial biopsies were obtained from osteoarthritis (OA; n = 9), chronic pyrophosphate arthropathy (CPPA; n = 7) or rheumatoid arthritis (RA; n = 8) patients. The histological inflammatory score was determined using a semi-quantitative scale based on synovial hyperplasia, lymphocytes, plasmocytes, neutrophils and macrophages infiltration. Proteomic analysis was performed by liquid chromatography-mass spectrometry (LC-MS/MS). Differentially expressed proteins were confirmed by immunohistochemistry. Out of the 1871 proteins identified and quantified by LC-MS/MS, 10 proteins (LAP3, MANF, LCP1, CTSZ, PTPRC, DNAJB11, EML4, SCARA5, EIF3K, C1orf123) were differentially expressed in the synovial membrane of at least one of the three disease groups (RA, OA and CPPA). Significant increased expression of the seven first proteins was detected in RA and correlated to the histological inflammatory score. Proteomics is therefore a powerful tool that provides a molecular pattern to the classical histology usually applied for synovitis characterization. Except for LCP1, CTSZ and PTPRC, all proteins have never been described in human synovitis.

Highlights

Stress proteins, mostly chaperones and co-chaperones, were increased in synovitis of OA, chronic pyrophosphate arthropathy (CPPA) and rheumatoid arthritis (RA) patients and that their expression levels were correlated with the histological inflammatory scoring based on the immune cell infiltration and hyperplasia [15]. In this proteomic study performed on the same patients as previously published [15], we further focus on proteins differentially expressed in the highly inflamed synovitis of RA patients compared to moderately inflamed CPPA and OA synovitis to better understand the inflammatory process that occurs in the tissue at the molecular level
Proteomic analysis of synovial tissue was a powerful tool to identify novel proteins expressed in the synovium of patients with articular disease
Except for lymphocyte cytosolic protein 1 (LCP1) [16,17], Cathepsin Z (CTSZ) [16] and PTPRC [18] previously identified in RA and OA

Summary

Introduction

The synovial membrane is a thin connective tissue that separates the joint capsule from the joint cavity. It contributes to cartilage nutrition and lubrication by maintaining synovial fluid volume and composition. It comprises two layers: the intima (the inner lining layer in contact with synovial fluid in the joint cavity) and subintima (the outer sublining layer in contact with the joint capsule). The intima consists of 1–2 cells thickness, including fibroblasts and resident macrophages, while the subintima is relatively acellular, 4.0/). Containing blood and lymphatic vessels, fibroblasts and few infiltrating cells in a collagenous extracellular matrix [1]. The synovial membrane is known for playing a major role in the inflammatory joint diseases such as rheumatoid arthritis (RA) and to a less extent in osteoarthritis (OA) [2]

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Results

Conclusion