Proteome analysis reveals disease-associated marker proteins to differentiate RA patients from other inflammatory joint diseases with the potential to monitor anti-TNFalpha therapy.
New experimental approaches of molecular medicine such as transcriptome and proteome analysis have been implemented in rheumatology research. Two-dimensional gel electrophoresis in combination with mass spectrometry was used to visualize and to identify proteins in synovial fluid (SF) and plasma samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The small calcium binding protein S100A9 (MRP14) was identified as a discriminatory marker protein in SF by global proteomic analysis. To confirm these results and to examine the reproducibility and the applicability as a diagnostic marker, levels of the S100A8 (MRP8)/A9 (MRP14) heterocomplex in plasma and in synovial fluid were validated from patients with RA, OA, and other inflammatory joint diseases using enzyme immunoassay techniques. It was found that plasma levels of the S100A8/A9 heterocomplex correlate well with levels in SF, and hence, determination of plasma levels can be used to distinguish RA patients from patients with other inflammatory joint diseases, as well as from OA patients and controls. Initial studies on RA patients also indicate that plasma levels of the S100A8/A9 heterocomplex are a useful marker in monitoring anti TNFalpha therapy.
Drynda
Susanne
S
Clinic of Rheumatology, University of Magdeburg, Sophie-von-Boetticher-Strasse 1, 39245 Vogelsang/Gommern, Germany.
Ringel
Bruno
B
Kekow
Monika
M
Kühne
Cornelia
C
Drynda
Andreas
A
Glocker
Michael O
MO
Thiesen
Hans-Jürgen
HJ
Kekow
Jörn
J
D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D016903:Drug Monitoring / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics; D015203:Reproducibility of Results; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000627:therapeutic use*
C435500:ABCC11 protein, human; C435501:ABCC12 protein, human; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha