AB0529 Rituximab therapy monitoring by mtor, autophagy-related ULK1, caspase 3, CDK-inhibitor P21, TNF alpha, and osteoclast-specific cathepsin K and gelatinase MMP-9 gene expression in the peripheral blood of rheumatoid arthritis patients

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Altered rates of cell proliferation and apoptosis were also observed in RA. We hypothesized that expression of the genes responsible for cell growth and proliferation (mTOR, p21), autophagy (ULK1), apoptosis (caspase 3), inflammation (TNFalpha), and bone resorption (cathepsin K and gelatinase MMP-9) measured in the peripheral blood could serve important biomarkers for anti-rheumatic therapy monitoring. Objectives To find peripheral blood gene expression indicators pointing to treatment efficacy of rituximab in RA patients. Methods 12 seropositive RA females aged 52±12.0 years old, disease duration 7.6±5.8 years (with previous failure to DMARD and anti-TNFalpha blockers) treated with rituximab (0.5-1g) for a single treatment course, and 47 healthy age-matched control femaleswere examined in this study. Clinical response was assessed by disease activity score (DAS) 28, erythrocyte sedimentation rate (ESR), serum levels of anti-CCP antibodies, C-reactive protein (CRP), and rheumatoid factor (RF). Bone erosion and joint space narrowing scores were monitored by X-ray analysis. Total RNA isolated from the peripheral blood was used in gene expression studies performed with quantitative Real-time RT-PCR. p70-S6K, p21, and caspase 3 protein levels were quantified by ELISA. Results Expression of all the examined genes measured in the peripheral blood was significantly upregulated (p