Abstract
BackgroundRheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints. Despite intense efforts, there are currently no definitive markers for early diagnosis of RA and for monitoring the progression of this disease, though some of the markers like anti CCP antibodies and anti vimentin antibodies are promising. We sought to catalogue the proteins present in the synovial fluid of patients with RA. It was done with the aim of identifying newer biomarkers, if any, that might prove promising in future.MethodsTo enrich the low abundance proteins, we undertook two approaches—multiple affinity removal system (MARS14) to deplete some of the most abundant proteins and lectin affinity chromatography for enrichment of glycoproteins. The peptides were analyzed by LC–MS/MS on a high resolution Fourier transform mass spectrometer.ResultsThis effort was the first total profiling of the synovial fluid proteome in RA that led to identification of 956 proteins. From the list, we identified a number of functionally significant proteins including vascular cell adhesion molecule-1, S100 proteins, AXL receptor protein tyrosine kinase, macrophage colony stimulating factor (M-CSF), programmed cell death ligand 2 (PDCD1LG2), TNF receptor 2, (TNFRSF1B) and many novel proteins including hyaluronan-binding protein 2, semaphorin 4A (SEMA4D) and osteoclast stimulating factor 1. Overall, our findings illustrate the complex and dynamic nature of RA in which multiple pathways seems to be participating actively.ConclusionsThe use of high resolution mass spectrometry thus, enabled identification of proteins which might be critical to the progression of RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-016-9113-1) contains supplementary material, which is available to authorized users.
Highlights
Rheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints
The use of high resolution mass spectrometry enabled identification of proteins which might be critical to the progression of RA
We identified several markers manifested in pannus formation that belong to the S100 family of proteins—notable ones include S100A11, S100A8 and S100A9 [8, 44]
Summary
Rheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints. We sought to catalogue the proteins present in the synovial fluid of patients with RA It was done with the aim of identifying newer biomarkers, if any, that might prove promising in future. The biology of the disease is highly complex and manifests as a cascade of events observed during progression of the disease. Some of these include development of autoantibodies referred to as the rheumatoid factor, appearance of anti-citrullinated protein antibodies and bone and cartilage erosion, which eventually leads to systemic manifestations including involvement of the cardiovascular system and the kidneys [2, 15, 16]. Progressive erosion of bone in the affected sites manifests as a pseudotumoral condition of the synovium called pannus where all these complex cascades of events occur [20]
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