Putative Association between Low Baseline Gene Expression in the Peripheral Blood and Clinical Remission in Rheumatoid Arthritis Patients Treated with Tofacitinib

Abstract

We investigated the importance of the baseline expression of genes involved in energy generation, as prognostic biomarkers of the treatment response to tofacitinib in patients with rheumatoid arthritis (RA). Peripheral blood samples were obtained from 28 patients with RA who received 3 months of tofacitinib therapy from 26 healthy controls. Clinical response was evaluated based on the disease activity score, the erythrocyte sedimentation rate (DAS28-ESR), and the serum levels of ACPA, RF, CRP, and ESR. Clinical remission was assessed based on DAS28 score <2.6. Protein concentrations were measured using ELISA. Total RNA isolated from whole blood was used for gene expression analysis using quantitative RT-PCR. All patients were diagnosed with Steinbrocker’s radiographic stage II-III at baseline, and most showed erosive arthritis with ACPA and RF positivity. Tofacitinib treatment significantly decreased the disease activity. Upon study completion, seven patients showed remission. Before and after TOFA therapy, a significantly higher expression of succinate dehydrogenase and pyruvate kinase genes was observed in all the examined patients compared to healthy subjects. However, the pre-therapy expression of these genes and corresponding proteins was significantly (p ≤ 0.05) lower in patients who showed remission than in other patients with RA. Moreover, we observed that, during follow-up, patients who developed remission showed an increasing trend in the expression of the examined genes, whereas the others showed some decreases in gene expression, although this was not statistically significant. We concluded that, compared with RA patients maintaining persistent moderate or high disease activity, those with clinical remission following tofacitinib treatment showed a significantly lower baseline expression of genes involved in energy generation.

Baseline Gene Expression Analysis in the Peripheral Blood of Patients With Rheumatoid Arthritis as an Important Supplement to Standard Composite Measure

“…In view of this, I, along with my co-authors, would like to add some mechanistic characteristics for standard composite disease activity status measures to monitor treatment response involving gene expression analyses in the peripheral blood mononuclear cells (PBMCs) of patients with RA prior to TOF treatment. Indeed, in our recent publication, 2 we proved the importance of baseline expression of genes involved in energy generation, as prognostic biomarkers for remission attainment after treatment of 28 patients with RA with TOF for 3 months. Clinical response was evaluated based on the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), and serum levels of anticitrullinated peptide antibodies, rheumatoid factor, C-reactive protein, and ESR.…”

Predicting the efficacy of tofacitinib therapy based on gene expression of proinflammatory cytokines and proteases in cultured blood cells of patients with rheumatoid arthritis

“…Поскольку периферическая кровь является самым доступным биоматериалом, а экспрессия генов -самой ранней клеточной реакцией организма на изменения окружающей среды [9], анализ экспрессии генов мононуклеарных клеток периферической крови (МКПК) может быть использован для оценки реакции пациента на терапию. Данные нашего ранее опубликованного исследования показали, что дости-жение клинической ремиссии у пациентов с РА, получавших TОФА, было связано с более низкой исходной экспрессией генов, участвующих в продукции энергии (пируваткиназы и сукцинатдегидрогеназы), по сравнению с остальными больными, в то время как отсутствие ответа на TОФА сопровождалось высокой базальной экспрессией этих генов [10].…”