Identification of RGS1 as a candidate biomarker for undifferentiated spondylarthritis by genome-wide expression profiling and real-time polymerase chain reaction.

Abstract

OBJECTIVE:

To compare gene expression profiles between ankylosing spondylitis (AS) and undifferentiated spondylarthritis (uSpA) patients with inflammatory low back pain.

METHODS:

Peripheral blood mononuclear cells (PBMCs) from patients with AS, patients with uSpA, and healthy subjects were screened using genome-wide microarrays, followed by validation by real-time polymerase chain reaction (PCR).

RESULTS:

Microarray profiling and real-time PCR assays showed only minor differences between AS patients and healthy subjects. In contrast, 20 genes were strikingly more highly expressed in uSpA patients. Regulator of G protein signaling 1 (RGS1) was identified as the most useful biomarker for distinguishing uSpA patients, and to a lesser extent AS patients, from control subjects (P = 2.3 x 10(-7) and 6.7 x 10(-3), respectively). These findings were verified in an independent cohort that also included patients with rheumatoid arthritis and patients with mechanical low back pain. The receiver operating characteristic area under the curve values in the first and second cohorts of uSpA patients were 0.99 and 0.93, respectively (P = 1 x 10(-4)). To evaluate the possible derivation of RGS1, we cultured a monocyte-derived cell line with a panel of cytokines and chemokines. RGS1 was significantly induced either by tumor necrosis factor alpha (TNFalpha) or by interleukin-17 (IL-17).

CONCLUSION:

Our findings indicate that uSpA PBMCs carry strikingly more highly expressed genes compared with PBMCs from AS patients or healthy subjects, and that TNFalpha- and IL-17-inducible RGS1 is a potential biomarker for uSpA, and to a lesser extent for AS, with inflammatory low back pain.

• Authors: Jieruo Gu, Yu-Ling Wei, James C C Wei, Feng Huang, Ming-Shiou Jan, Michael Centola, Mark B Frank, David Yu
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 60 Issue 11 Pg. 3269-79 (Nov 2009) ISSN: 0004-3591 [Print] United States
• PMID: 19877080 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Interleukin-17
• RGS Proteins
• RGS1 protein, human
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Biomarkers (blood)
• Case-Control Studies
• Cells, Cultured
• Diagnosis, Differential
• Female
• Gene Expression Profiling
• Humans
• Interleukin-17 (pharmacology)
• Leukocytes, Mononuclear (drug effects, metabolism, pathology)
• Male
• Middle Aged
• RGS Proteins (blood)
• Reverse Transcriptase Polymerase Chain Reaction
• Spondylarthritis (blood, diagnosis)
• Spondylitis, Ankylosing (blood, diagnosis)
• Tumor Necrosis Factor-alpha (pharmacology)