Constitutive STAT 3 Phosphorylation in Circulating CD 4 + T Lymphocytes Associates with Disease Activity and Treatment Response in Recent-Onset Rheumatoid Arthritis

The aim of the present study was to examine constitutive signal transducer and activator of transcription 3 (STAT3) phosphorylation in circulating leukocytes as a candidate biomarker in rheumatoid arthritis (RA). 25 patients with recent-onset, untreated RA provided samples for whole blood flow cytometric determination of intracellular STAT3 phosphorylation, expressed as relative fluorescence units. The occurrence of constitutive STAT3 phosphorylation was evaluated by determining proportion of STAT3-phosphorylated cells among different leukocyte subtypes. Plasma levels of interleukin (IL)-6, IL-17 and IL-21 were measured by immunoassay, radiographs of hands and feet were examined and disease activity score (DAS28) was determined. Biomarkers were restudied and treatment response (according to European League Against Rheumatism) was determined after 12 months of treatment with disease-modifying antirheumatic drugs. At baseline, constitutive phosphorylation of STAT3 occurred in CD4 T cells of 14 (56%) patients, CD8 T cells of 13 (52%) patients, in CD19 B cells of 7 (28%) patients, and in CD14 monocytes of 12 (48%) patients. STAT3 phosphorylation levels of CD4 T cells associated with DAS28, and those of all leukocyte subtypes studied associated with erosive disease. The presence of constitutive STAT3 phosphorylation in CD4 T lymphocytes, pSTAT3 fluorescence intensity of CD4 and CD8 T cells and C-reactive protein (CRP) levels at baseline associated with good treatment response. In conclusion, constitutive STAT3 phosphorylation in circulating CD4 T cells is common in recent-onset untreated RA and associates with good treatment response in patients characterized by high disease activity and the presence of systemic inflammation. PLOS ONE | DOI:10.1371/journal.pone. 0137385 September 9, 2015 1 / 15 OPEN ACCESS Citation: Kuuliala K, Kuuliala A, Koivuniemi R, Oksanen S, Hämäläinen M, Moilanen E, et al. (2015) Constitutive STAT3 Phosphorylation in Circulating CD4 T Lymphocytes Associates with Disease Activity and Treatment Response in Recent-Onset Rheumatoid Arthritis. PLoS ONE 10(9): e0137385. doi:10.1371/journal.pone. 0137385 Editor: Oreste Gualillo, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab, Research Laboratory 9, Santiago University Clinical Hospital. Santiago de Compostela, SPAIN Received: March 31, 2015 Accepted: August 16, 2015 Published: September 9, 2015 Copyright: © 2015 Kuuliala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: This work was supported by Paulo Foundation and Finnish Cultural Foundation (to KK); Helsinki University Central Hospital Research Funds (to MLR and HR); and Finska Läkaresällskapet (to MLR and HR). The funders had no role in study