PMID- 22838733 OWN - NLM STAT- MEDLINE DCOM- 20150622 LR - 20211021 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 14 IP - 4 DP - 2012 Jul 27 TI - Monocyte populations as markers of response to adalimumab plus MTX in rheumatoid arthritis. PG - R175 LID - 10.1186/ar3928 [doi] AB - INTRODUCTION: The treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNFalpha) 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-TNFalpha 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-TNFalpha 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-TNFalpha treatment in patients with RA. FAU - Chara, Luis AU - Chara L FAU - Sanchez-Atrio, Ana AU - Sanchez-Atrio A FAU - Perez, Ana AU - Perez A FAU - Cuende, Eduardo AU - Cuende E FAU - Albarran, Fernando AU - Albarran F FAU - Turrion, Ana AU - Turrion A FAU - Chevarria, Julio AU - Chevarria J FAU - Sanchez, Miguel A AU - Sanchez MA FAU - Monserrat, Jorge AU - Monserrat J FAU - de la Hera, Antonio AU - de la Hera A FAU - Prieto, Alfredo AU - Prieto A FAU - Sanz, Ignacio AU - Sanz I FAU - Diaz, David AU - Diaz D FAU - Alvarez-Mon, Melchor AU - Alvarez-Mon M LA - eng GR - R37 AI049660/AI/NIAID NIH HHS/United States GR - U19 AI056390/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120727 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - 0 (Biomarkers) RN - 0 (Tumor Necrosis Factor-alpha) RN - FYS6T7F842 (Adalimumab) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adalimumab MH - Adult MH - Antibodies, Monoclonal, Humanized/*administration & dosage MH - Antirheumatic Agents/*administration & dosage MH - Arthritis, Rheumatoid/blood/*drug therapy MH - Biomarkers/blood MH - Drug Therapy, Combination MH - Female MH - Humans MH - Male MH - Methotrexate/*administration & dosage MH - Middle Aged MH - Monocytes/*drug effects/metabolism MH - Prospective Studies MH - Treatment Outcome MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors PMC - PMC3580569 EDAT- 2012/07/31 06:00 MHDA- 2015/06/24 06:00 PMCR- 2012/07/27 CRDT- 2012/07/31 06:00 PHST- 2012/02/24 00:00 [received] PHST- 2012/07/27 00:00 [accepted] PHST- 2012/07/31 06:00 [entrez] PHST- 2012/07/31 06:00 [pubmed] PHST- 2015/06/24 06:00 [medline] PHST- 2012/07/27 00:00 [pmc-release] AID - ar3928 [pii] AID - 10.1186/ar3928 [doi] PST - epublish SO - Arthritis Res Ther. 2012 Jul 27;14(4):R175. doi: 10.1186/ar3928.