Abstract
IntroductionThe treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNFα) biological drugs has dramatically improved the prognosis of these patients. However, a third of the treated patients do not respond to this therapy. Thus, the search for biomarkers of clinical response to these agents is currently highly active. Our aim is to analyze the number and distribution of circulating monocytes, and of their CD14+highCD16-, CD14+highCD16+ and CD14+lowCD16+ subsets in methotrexate (MTX) non-responder patients with RA, and to determine their value in predicting the clinical response to adalimumab plus MTX treatment.MethodsThis prospective work investigated the number of circulating monocytes, and of their CD14+highCD16-, CD14+highCD16+ and CD14+lowCD16+ subsets, in 35 MTX non-responder patients with RA before and after three and six months of anti-TNFα treatment using multiparametric flow cytometry. The number of circulating monocytes in an age- and sex-matched healthy population was monitored as a control.ResultsNon-responder patients with RA show an increased number of monocytes and of their CD14+highCD16-, CD14+highCD16+ and CD14+lowCD16+ subsets after three months of adalimumab plus MTX treatment that remained significantly increased at six months. In contrast, significant normalization of the numbers of circulating monocytes was found in responders at three months of adalimumab plus MTX treatment that lasts up to six months. CX3CR1 expression is increased in monocytes in non-responders. At three months of anti-TNFα treatment the number of circulating monocytes and their subsets was associated with at least 80% sensitivity, 84% specificity and an 86% positive predictive value (PPV) in terms of discriminating between eventual early responders and non-responders.ConclusionsThe absolute number of circulating monocytes and of their CD14+highCD16-, CD14+highCD16+ and CD14+lowCD16+ subsets at three months of adalimumab plus MTX treatment, have a predictive value (with high specificity and sensitivity) in terms of the clinical response after six months of anti-TNFα treatment in patients with RA.
Highlights
The treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNFa) biological drugs has dramatically improved the prognosis of these patients
Non-responder patients with RA show an increased number of monocytes and of their CD14+highCD16, CD14+highCD16+ and CD14+lowCD16+ subsets after three months of adalimumab plus MTX treatment that remained significantly increased at six months
We included in the study 13 patients who were age ≥18 years, had a diagnosis of RA according to the 1987 revised European League Against Rheumatism (EULAR) criteria [18], had a Disease Activity Score 28 (DAS28) according to EULAR criteria of more than 2.5 [18], and were untreated with disease-modifying antirheumatic drugs (DMARDS)
Summary
The treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNFa) biological drugs has dramatically improved the prognosis of these patients. The minoritarian subsets (10% of the circulating monocytes) are characterized by the expression of CD16 plus either high or low levels of CD14 (intermediate CD14+highCD16+ monocytes and CD14+lowCD16+ non-classical monocytes, respectively) [11] These three phenotypically defined monocyte subsets show different functional properties, such as patterns of cytokine secretion and chemokine receptor expression, and migratory properties into normal and inflamed tissue. These three different monocyte subsets differ in their ability to differentiate into effector cells, including macrophages, dendritic cells and osteoclasts [8,9,10]. Monocytes and monocyte derived cells appear to be involved in the pathogenesis of RA [12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
