Research article

Identification of blood biomarkers of rheumatoid arthritis by transcript profiling of peripheral blood mononuclear cells from the rat collagen-induced arthritis model

Jianyong Shou^1,2 , Christopher M Bull¹, Li Li¹, Hui-Rong Qian³, Tao Wei¹, Shuang Luo¹, Douglas Perkins¹, Patricia J Solenberg¹, Seng-Lai Tan⁴, Xin-Yi Cynthia Chen⁴, Neal W Roehm⁵, Jeffrey A Wolos¹ and Jude E Onyia¹

¹Integrative Biology, Lilly Research Laboratories, Indianapolis, Indiana, USA

²Angiogenesis and Tumor Microenvironment Biology, Lilly Research Laboratories, Indianapolis, Indiana, USA

³Statistics, Lilly Research Laboratories, Indianapolis, Indiana, USA

⁴Cancer Inflammation and Cell Survival, Lilly Research Laboratories, Indianapolis, Indiana, USA

⁵Platform/CFARS, Lilly Research Laboratories, Indianapolis, Indiana, USA

author email corresponding author email

Arthritis Research & Therapy 2006, 8:R28doi:10.1186/ar1883

Published:	10 January 2006

Abstract

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease that results in joint destruction and subsequent loss of function. To better understand its pathogenesis and to facilitate the search for novel RA therapeutics, we profiled the rat model of collagen-induced arthritis (CIA) to discover and characterize blood biomarkers for RA. Peripheral blood mononuclear cells (PBMCs) were purified using a Ficoll gradient at various time points after type II collagen immunization for RNA preparation. Total RNA was processed for a microarray analysis using Affymetrix GeneChip technology. Statistical comparison analyses identified differentially expressed genes that distinguished CIA from control rats. Clustering analyses indicated that gene expression patterns correlated with laboratory indices of disease progression. A set of 28 probe sets showed significant differences in expression between blood from arthritic rats and that from controls at the earliest time after induction, and the difference persisted for the entire time course. Gene Ontology comparison of the present study with previous published murine microarray studies showed conserved Biological Processes during disease induction between the local joint and PBMC responses. Genes known to be involved in autoimmune response and arthritis, such as those encoding Galectin-3, Versican, and Socs3, were identified and validated by quantitative TaqMan RT-PCR analysis using independent blood samples. Finally, immunoblot analysis confirmed that Galectin-3 was secreted over time in plasma as well as in supernatant of cultured tissue synoviocytes of the arthritic rats, which is consistent with disease progression. Our data indicate that gene expression in PBMCs from the CIA model can be utilized to identify candidate blood biomarkers for RA.