Identification of autoantibodies against transthyretin for the screening and diagnosis of rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic and inflammatory rheumatic disease that leads to inflammation of the joints and surrounding tissues. Identification of novel protein(s) associated with severity of RA is a prerequisite for better understanding of pathogenesis of this disease that may also have potential to serve as novel biomarkers in the diagnosis of RA. Present study was undertaken to compare the amount of autoantigens and autoantibodies in the plasma of RA patients in comparison to healthy controls. Plasma samples were collected from the patients suffering from RA, Osteoarthritis (OA), Systemic lupus erythematosus (SLE) and healthy volunteers. The screening of plasma proteins were carried out using 2-dimensional gel electrophoresis followed by identification of differentially expressed protein by MALDI-TOF MS/MS. Among several differentially expressed proteins, transthyretin (TTR) has been identified as one of the protein that showed significantly up regulated expression in the plasma of RA patients. The results were further validated by Western blot analysis and ELISA. In comparison to OA synovium, an exclusive significantly high expression of TTR in RA has been validated through IHC, Western blotting and IEM studies. Most importantly, the increase in expression of TTR with the progression of severity of RA condition has been observed. The autoantibodies against TTR present in the RA plasma were identified using immunoprecipitation-Western methods. The significant production of autoantibodies was validated by ELISA and Western blot analysis using recombinant pure protein of TTR. Hence, these novel observations on increase in TTR expression with the increase in severity of RA conditions and significant production of autoantibodies against TTR clearly suggest that a systematic studies on the role TTR in the pathogenesis of RA is immediately required and TTR may be used as a serum diagnostic marker together with other biochemical parameters and clinical symptoms for RA screening and diagnosis.
Department of Genomics & Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi, India; Department of Environmental Studies, Delhi University, Delhi, India.
Saurabh
S
Sharma
Department of Genomics & Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
Sreejoyee
S
Ghosh
Department of Genomics & Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
Lalit Kumar
LK
Singh
Department of Genomics & Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
Ashish
A
Sarkar
Department of Orthopaedic, All India Institute of Medical Sciences, New Delhi, India.
Rajesh
R
Malhotra
Department of Clinical Immunology and Rheumatology, Army Hospital (Research and Referral), New Delhi, India.
Onkar Prasad
OP
Garg
Department of Genomics & Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
Yogendra
Y
Singh
Department of Environmental Studies, Delhi University, Delhi, India.
Radhey Shyam
RS
Sharma
Department of Clinical Immunology and Rheumatology, Army Hospital (Research and Referral), New Delhi, India.
Darshan Singh
DS
Bhakuni
Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Taposh Kumar
TK
Das
Department of Genomics & Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
Sagarika
S
Biswas
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology; D011228:Prealbumin / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; D015415:Biomarkers; D011228:Prealbumin