Constitutive STAT3 Phosphorylation in Circulating CD4+ T Lymphocytes Associates with Disease Activity and Treatment Response in Recent-Onset Rheumatoid Arthritis
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Updated: Apr 4, 2026

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
Krista Kuuliala1, Antti Kuuliala1, Riitta Koivuniemi2
1Bacteriology and Immunology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Abstract:
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.
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