Proteomics in rheumatology: The beginning of a fairy tale?

Abstract

One of the major challenges in proteome research is to translate its applications to the setting of human diseases. Proteomics in rheumatology is an area with marked potential including applications ranging from diagnostics, over therapeutic monitoring to discovery of new potential therapeutic targets. Biomarkers will be essential to discriminate between clinical similar rheumatic diseases, to monitor disease-states or to install the best appropriate therapy. Especially in the field of rheumatology, analysis of specific genes and/or their expression products by pharmacogenetics/-genomics or pharmacoproteomics could be necessary to enable an effective, patient-tailored therapy. In rheumatology, direct examination of proteins may be of utmost importance, as it is already known that PTMs, such as citrullination of proteins or peptides, may be involved in certain rheumatic diseases. The discovery and validation of antibodies directed against citrullinated proteins/peptides in rheumatic diseases using proteome analysis approaches has been described. Gel-free methods, SELDI-approaches and classic 2-DE approaches have been deployed on body fluids as well as on target tissues in different rheumatic diseases. Proteomics in rheumatology is on the rise and pilot studies have indicated that the application of proteomicsbased technologies in rheumatic diseases appears to be an exciting example of translational research.

Autoantigens: Novel forms and presentation to the immune system

“…Finally, a third citrullinated substrate, CCP3, has been developed that assays IgG specific ACPA. The sensitivity and specificity of CCP2 tests have been reported to be 90 and 98%, respectively [95,97]. As published extensively, the detection of anti-CCP in patient sera can predict the onset of RA and various clinical sequelae.…”

“…More importantly, in the case of RA, PADs (PAD1, PAD2, PAD3, PAD4) are highly activated in the presence of Ca2 þ ion deposition in an inflamed joint during apoptotic cell death [7,94] lead to the generation high level of citrullinated protein/peptide. Anti-citrullinated protein/peptide antibody (ACPA) has proven to be extremely specific to RA [95][96][97], and anticitrulline-containing epitope serum antibody has been used clinically as a diagnostic tool to detect the onset of RA [96,98]. A CCP construct is commonly used as the diagnostic test to detect APCAs.…”

Subchondral bone proteomics in osteoarthritis: Current status and perspectives

“…Proteomics, a large-scale analysis of proteins that involves isolation, purification, and mass spectrometry of proteins of interest, makes it possible to search such factors or mediators in a systemic fashion. Proteomic technologies have been widely adopted in studying various rheumatic diseases [4] , [5] , [6] , [7] , [8] , [9] , [10] . Development of high-throughput and high sensitivity mass spectrometry has opened a door to look into the proteins and peptides contained in body fluids and joint tissues [11] , [12] .…”

Proteomic Studies in Rheumatology

“…Появле-ние высокотехнологичных методов, позволя-ющих идентифицировать первичную структу-ру и посттрансляционные модификации бел-ка, определить белковый состав биологиче-ских объектов, обусловило быстрое развитие протеомики [4]. Протеомные исследования в ревматологии могут преследовать ряд задач, таких как поиск диагностических биомарке-ров, идентификация терапевтических мише-ней и разработка методов оценки эффектив-ности терапии [5].…”