title: Analysis of CXCR5+Th17 cells in relation to disease activity and TNF inhibitor therapy in Rheumatoid Arthritis.
abstract: Th17 and TfH cells are thought to promote tissue inflammation and autoantibody production, respectively, in autoimmune diseases including rheumatoid arthritis (RA). TfH cells that co-express Th17 markers (CXCR5+Th17) encompass both of these pathogenic functions, and are increased in some human autoimmune settings including juvenile dermatomyositis. We investigated CXCR5+Th17 cells in RA subjects with stable or active disease and before and after TNF inhibitor therapy. CXCR5+Th17 cell frequency was increased in RA compared to healthy controls, but other helper T cell subsets were not different. CXCR5+Th17 cells correlated with disease activity in subjects with active RA prior to initiation of TNF inhibitor therapy. Baseline CXCR5+Th17 cells also correlated with numbers of swollen joints as late as one year post-therapy. CXCR5+Th17 cell frequencies were unaltered by TNF blockade and in fact remained remarkably stable within individuals. We conclude that CXCR5+Th17 cells are not a direct target of TNF blockade and therefore cannot serve as a biomarker of current disease activity. However, basal CXCR5+Th17 cell frequency may indicate underlying differences in disease phenotype between patients and predict ultimate success of TNF inhibitor therapy.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Pittsburgh, 3500 Terrace St, Pittsburgh, PA 15261, USA.
authors.forename: Deepika
authors.initials: D
authors.lastname: Singh
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Pittsburgh, 3500 Terrace St, Pittsburgh, PA 15261, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Henkel
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Pittsburgh, 3500 Terrace St, Pittsburgh, PA 15261, USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Sendon
authors.affiliation: Epidemiology Data Coordinating Center, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, Pittsburgh, PA 15261, USA.
authors.forename: June
authors.initials: J
authors.lastname: Feng
authors.affiliation: Epidemiology Data Coordinating Center, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, Pittsburgh, PA 15261, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Fabio
authors.affiliation: Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh, PA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Metes
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Pittsburgh, 3500 Terrace St, Pittsburgh, PA 15261, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Moreland
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Pittsburgh, 3500 Terrace St, Pittsburgh, PA 15261, USA.
authors.forename: Mandy J
authors.initials: MJ
authors.lastname: McGeachy
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D054380:Receptors, CXCR5 / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D015415:Biomarkers; C095085:CXCR5 protein, human; D054380:Receptors, CXCR5; D014409:Tumor Necrosis Factor-alpha