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