Monitoring of Peripheral Blood Leukocytes and Plasma Samples: A Pilot Study to Examine Treatment Response to Leflunomide in Rheumatoid Arthritis.

Lycia M G Da Silva,Robinson Sabino-Silva,Anita M R Fernandes,Douglas Carvalho Caixeta,João B Calixto,Liziane C M Da Silva,Valério Monteiro-Neto,Jaqueline P Pontes,Cristiane Silva E Silva,Marcos A G Grisotto,Juliano Ferreira,Leia Cardoso-Sousa,Pedro S Carvalho Júnior,Mahiba M R S Martins,Alisson S Henrique,Debora D Lückemeyer,João F S Rodrigues,Elizabeth S Fernandes,Juliana S S Macedo

doi:10.3390/ph14020106

Abstract

Rheumatoid arthritis (RA) is a painful inflammatory disease of the joints which affects a considerable proportion of the world population, mostly women. If not adequately treated, RA patients can become permanently disabled. Importantly, not all the patients respond to the available anti-rheumatic therapies, which also present diverse side effects. In this context, monitoring of treatment response is pivotal to avoid unnecessary side effects and costs towards an ineffective therapy. Herein, we performed a pilot study to investigate the potential use of flow cytometry and attenuated total reflection–Fourier transform infrared (ATR-FTIR) spectroscopy as measures to identify responders and non-responders to leflunomide, a disease-modifying drug used in the treatment of RA patients. The evaluation of peripheral blood CD62L+ polymorphonuclear cell numbers and ATR-FTIR vibrational modes in plasma were able to discriminate responders to leflunomide (LFN) three-months after therapy has started. Overall, the results indicate that both flow cytometry and ATR-FTIR can potentially be employed as additional measures to monitor early treatment response to LFN in RA patients.

Highlights

Rheumatoid arthritis (RA) is a painful inflammatory disease of the joints which affects~0.5–1% of the world population, mostly women
We performed a pilot study to evaluate the potential applicability of ATRFTIR spectroscopy of plasma samples and flow cytometry analysis of peripheral blood leukocytes to monitor treatment response to LFN in rheumatoid arthritis (RA) patients
C-reactive protein and rheumatoid factor levels. They exhibited augmented numbers of peripheral blood leukocytes, and reduced expression of the L-selectin CD62L on CD14+ cells and PMNs. These results are in accordance with previous reports as leukocytes shed CD62L when they become activated, a process which has been linked to cell migration to inflamed sites [24,25]

Summary

Introduction

Rheumatoid arthritis (RA) is a painful inflammatory disease of the joints which affects~0.5–1% of the world population, mostly women. Rheumatoid arthritis (RA) is a painful inflammatory disease of the joints which affects. Pharmaceuticals 2021, 14, 106 permanently disabled due to the intense articular pain, stiffness and oedema resulting from chronic joint inflammation. In addition to the joint pathology, RA patients frequently suffer from systemic alterations such as anemia. Despite its morbidity and prevalence, the currently available anti-rheumatic therapy does not halt disease progression. International guidelines for early RA recommend treatment to be started as soon as possible with disease-modifying drugs (DMARDs). Methotrexate is used as the first treatment strategy for RA; other DMARDs such as leflunomide (LFN) have been largely prescribed to those with contraindication to methotrexate [1]. It is estimated that 5–10% of RA patients do not improve with LFN following a six-month treatment [4]

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Discussion

Conclusion