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Patients with long-term, treated, rheumatoid arthritis (RA) show abnormalities in their circulating CD4+ T-lymphocytes, but whether this occurs in recently diagnosed na&iuml, ve patients to disease-modifying drugs (DMARDs) is under discussion. These patients show heterogeneous clinical response to methotrexate (MTX) treatment. We have examined the count of circulating CD4+ T-lymphocytes, and their na&iuml, ve (TN), central memory (TCM), effector memory (TEM) and effector (TE) subsets, CD28 expression and V&beta, TCR repertoire distribution by polychromatic flow cytometry in a population of 68 DMARD-na&iuml, ve recently diagnosed RA patients, before and after 3 and 6 months of MTX treatment. At pre-treatment baseline, patients showed an expansion of the counts of CD4+ TN, TEM, TE and TCM lymphocyte subsets, and of total CD4+CD28&minus, cells and of the TE subset with a different pattern of numbers in MTX responder and non-responders. The expansion of CD4+TEM lymphocytes showed a predictive value of MTX non-response. MTX treatment was associated to different modifications in the counts of the CD4+ subsets and of the V&beta, TCR repertoire family distribution and in the level of CD28 expression in responders and non-responders. In conclusion, the disturbance of CD4+ lymphocytes is already found in DMARD-na&iuml, ve RA patients with different patterns of alterations in MTX responders and non-responders.

Introduction The 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. Methods This 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. Results 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. 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. Conclusions The 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.

Background The aim of this work was to analyze the number and distribution of circulating monocytes, and of their CD14+highCD16−, CD14+highCD16+ and CD14+lowCD16+ subset cells, in treatment-naive patients with rheumatoid arthritis (RA), and to determine their value in predicting the clinical response to methotrexate (MTX) treatment. Methods This prospective work investigated the number of circulating monocytes, and the numbers of CD14+highCD16−, CD14+highCD16+ and CD14+lowCD16+ subset cells, in 52 untreated patients with RA before MTX treatment, and at 3 and 6 months into treatment, using flow cytometry. Results The absolute number of circulating monocytes, and the numbers of CD14+highCD16−, CD14+highCD16+ and CD14+lowCD16+ subset cells, were significantly higher in MTX non-responders than in responders and healthy controls before starting and throughout treatment. Responders showed normal numbers of monocytes, and of their subset cells, over the study period. The pre-treatment absolute number of circulating monocytes, and the numbers of CD14+highCD16− and CD14+highCD16+ subset cells, were found to be predictive of the clinical response to MTX, with a sensitivity and specificity of >70% and >88%, respectively. Conclusions Treatment-naive patients with RA showed an anomalous distribution of circulating monocyte subsets, and an anomalous number of cells in each subset. A higher pre-treatment number of circulating monocytes, and higher numbers of CD14+highCD16− and CD14+highCD16+ subset cells, predict a reduced clinical response to MTX in untreated patients with RA. Electronic supplementary material The online version of this article (doi:10.1186/s12967-014-0375-y) contains supplementary material, which is available to authorized users.