Selective involvement of ERK and JNK mitogen-activated protein kinases in early rheumatoid arthritis (1987 ACR criteria compared to 2010 ACR/EULAR criteria): a prospective study aimed at identification of diagnostic and prognostic biomarkers as well as therapeutic targets

To investigate the expression and activation of mitogen-activated protein kinases in patients with early arthritis who are disease-modifying antirheumatic drug (DMARD) naïve. A total of 50 patients with early arthritis who were DMARD naïve (disease duration <1 year) were prospectively followed an...

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Bibliographic Details
Published in:	Annals of the rheumatic diseases Vol. 71; no. 3; p. 415
Main Authors:	de Launay, Daphne, van de Sande, Marleen G H, de Hair, Maria J H, Grabiec, Aleksander M, van de Sande, Gijs P M, Lehmann, K Aad, Wijbrandts, Carla A, van Baarsen, Lisa G M, Gerlag, Danielle M, Tak, Paul P, Reedquist, Kris A
Format:	Journal Article
Language:	English
Published:	England 01-03-2012
Subjects:	Adult Aged Aged, 80 and over Arthritis, Rheumatoid - diagnosis Arthritis, Rheumatoid - enzymology Arthritis, Rheumatoid - genetics Biomarkers - metabolism Disease Progression Early Diagnosis Enzyme Activation Extracellular Signal-Regulated MAP Kinases - genetics Extracellular Signal-Regulated MAP Kinases - metabolism Female Gene Expression Profiling - methods Gene Expression Regulation, Enzymologic Humans JNK Mitogen-Activated Protein Kinases - genetics JNK Mitogen-Activated Protein Kinases - metabolism Male Middle Aged Molecular Targeted Therapy - methods p38 Mitogen-Activated Protein Kinases - genetics p38 Mitogen-Activated Protein Kinases - metabolism Phosphorylation Prognosis Prospective Studies RNA, Messenger - genetics Severity of Illness Index Synovial Membrane - enzymology Young Adult
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Summary:	To investigate the expression and activation of mitogen-activated protein kinases in patients with early arthritis who are disease-modifying antirheumatic drug (DMARD) naïve. A total of 50 patients with early arthritis who were DMARD naïve (disease duration <1 year) were prospectively followed and diagnosed at baseline and after 2 years for undifferentiated arthritis (UA), rheumatoid arthritis (RA) (1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria), or spondyloarthritis (SpA). Synovial biopsies obtained at baseline were examined for expression and phosphorylation of p38, extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) by immunohistochemistry and digital analysis. Synovial tissue mRNA expression was measured by quantitative PCR (qPCR). ERK and JNK activation was enhanced at inclusion in patients meeting RA criteria compared to other diagnoses. JNK activation was enhanced in patients diagnosed as having UA at baseline who eventually fulfilled 1987 ACR RA criteria compared to those who remained UA, and in patients with RA fulfilling 2010 ACR/EULAR criteria at baseline. ERK and JNK activation was enhanced in patients with RA developing progressive joint destruction. JNK activation in UA predicted 1987 ACR RA classification criteria fulfilment (R(2)=0.59, p=0.02) after follow-up, and disease progression in early arthritis (R(2)=0.16, p<0.05). Enhanced JNK activation in patients with persistent disease was associated with altered synovial expression of extracellular matrix components and CD44. JNK activation is elevated in RA before 1987 ACR RA classification criteria are met and predicts development of erosive disease in early arthritis, suggesting JNK may represent an attractive target in treating RA early in the disease process.
ISSN:	1468-2060
DOI:	10.1136/ard.2010.143529