Constitutive STAT3 Phosphorylation in Circulating CD4+ 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.
Bacteriology and Immunology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Krista
K
Kuuliala
Bacteriology and Immunology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Antti
A
Kuuliala
Rheumatology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Riitta
R
Koivuniemi
Bacteriology and Immunology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Suvi
S
Oksanen
Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
Mari
M
Hämäläinen
Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
Eeva
E
Moilanen
Primary Health Care, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; General Practice, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Unit of Primary Health Care, Kuopio University Hospital, Kuopio, Finland.
Hannu
H
Kautiainen
Bacteriology and Immunology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Rheumatology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Marjatta
M
Leirisalo-Repo
Bacteriology and Immunology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Heikki
H
Repo
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000097:blood* / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D018501:Antirheumatic Agents; D016207:Cytokines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human