Synovial fluid proteome in rheumatoid arthritis.
BACKGROUND
Rheumatoid 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.


METHODS
To 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.


RESULTS
This 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.


CONCLUSIONS
The use of high resolution mass spectrometry thus, enabled identification of proteins which might be critical to the progression of RA.
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Amrita School of Biotechnology, Amrita University, Kollam, 690525 India.
Mitali
M
Bhattacharjee
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Department of Biotechnology, Kuvempu University, Shankaraghatta, 577451 India.
Lavanya
L
Balakrishnan
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Amrita School of Biotechnology, Amrita University, Kollam, 690525 India.
Santosh
S
Renuse
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Manipal University, Madhav Nagar, Manipal, 576104 India.
Jayshree
J
Advani
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Department of Biotechnology, Kuvempu University, Shankaraghatta, 577451 India.
Renu
R
Goel
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Manipal University, Madhav Nagar, Manipal, 576104 India.
Gajanan
G
Sathe
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Amrita School of Biotechnology, Amrita University, Kollam, 690525 India.
T S
TS
Keshava Prasad
Amrita School of Biotechnology, Amrita University, Kollam, 690525 India.
Bipin
B
Nair
Department of Rheumatology, Fortis Hospital, Bangalore, 560066 India.
Ramesh
R
Jois
Department of Rheumatology, Medical Division, Command Hospital (Air Force), Bangalore, 560007 India.
Subramanian
S
Shankar
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, BRB 527, Baltimore, MD 21205 USA ; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA ; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
Akhilesh
A
Pandey
Angiogenesis; Apoptosis; Bone repair; Hyaluronic acid; Lubricant; Neovascularisation; Osteoclastogenesis