Baseline JAK phosphorylation profile of peripheral blood leukocytes, studied by whole blood phosphospecific flow cytometry, is associated with 1-year treatment response in early rheumatoid arthritis

Krista Kuuliala,Riitta Koivuniemi,Antti Kuuliala,Marjatta Leirisalo-Repo,Hannu Kautiainen,Heikki Repo

doi:10.1186/s13075-017-1278-0

Abstract

BackgroundWe found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4+ T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA.MethodsThirty-five DMARD-naïve patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes. Treatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as absence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used to investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were estimated by bias-corrected bootstrapping.ResultsHigh JAK3 phosphorylation in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes and low JAK2 phosphorylation in CD14+ monocytes were significantly associated with remission following treatment with synthetic DMARDs.ConclusionsBaseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA.

Highlights

We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4+ T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs)
We found that baseline phosphorylation of STAT3 in whole blood leukocytes is associated with the treatment response achieved by use of Synthetic disease-modifying antirheumatic drug (sDMARD) [10]
The results of the present study show that high baseline JAK3 phosphorylation in all peripheral blood leukocyte subtypes studied (i.e., CD4+ and CD8+ T cells, B cells, and monocytes) is associated with remission achieved by sDMARDs among patients with early untreated RA

Summary

Introduction

We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4+ T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). Highly selective immunological agents have been developed for the treatment of RA, including biological disease-modifying antirheumatic drugs (DMARDs), especially blockers of inflammatory cytokines and immune cell surface receptors [5], and agents inhibiting intracellular signal transduction pathway members. As to the latter, Janus kinases (JAKs) are tempting targets because they are required for classical immune cytokine receptor signal transduction and are involved in the pathophysiology of several inflammatory and immune disorders [6, 7]. Despite the multiple drug options for treatment of RA, the lack of reliable predictive biomarkers poses a challenge to finding the most effective and suitable treatment for each individual rapidly, preferably within 3–4 months from the onset of symptoms [8]

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Discussion

Conclusion