Open AccessIdentification of RGS1 as a candidate biomarker for undifferentiated spondylarthritis by genome‐wide expression profiling and real‐time polymerase chain reaction
Author(s) -
Gu Jieruo,
Wei YuLing,
Wei James C. C.,
Huang Feng,
Jan MingShiou,
Centola Michael,
Frank Mark B.,
Yu David
Publication year - 2009
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24968
Subject(s) - biomarker , medicine , immunology , peripheral blood mononuclear cell , tumor necrosis factor alpha , erythrocyte sedimentation rate , gene expression profiling , gene expression , biology , gene , in vitro , biochemistry
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 × 10 −7 and 6.7 × 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 × 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 α (TNFα) 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 TNFα‐ and IL‐17–inducible RGS1 is a potential biomarker for uSpA, and to a lesser extent for AS, with inflammatory low back pain.