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      Increased frequency of peripheral blood follicular helper T cells and elevated serum IL-21 levels in patients with knee osteoarthritis

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          Abstract

          An aberrant immune response has been implicated in the pathogenesis of osteoarthritis (OA). However, the role of peripheral blood follicular helper T (TFH) cells in the pathogenesis of OA has yet to be elucidated. The purpose of the present study was to examine the role of TFH cells and serum interleukin-21 (IL-21) in the pathogenesis of OA. Frequency of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD-1)+, and IL-21+ CXCR5+CD4+ T cells in 40 patients with OA and 13 healthy controls (HCs) were examined by flow cytometry. The disease state in individual patients was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Concentrations of serum IL-21, interferon-γ (INF-γ), IL-4, IL-17A, and C-reactive protein (CRP) were determined, and the erythrocyte sedimentation rate (ESR) was measured. The percentages of CXCR5+CD4+ cells, PD-1+CXCR5+CD4+, ICOS+CXCR5+CD4+ and IL-21+CXCR5+CD4+ T cells in OA patients were significantly higher than those in the HCs. Furthermore, serum IL-21, IL-17A and IFN-γ levels in OA patients were significantly higher than those in HCs. Expression of IL-21+TFH cells in OA patients demonstrated a positive correlation with OA disease activity, CRP levels and WOMAC. TFH cells and IL-21 appear to serve an important role in the progression of OA. IL-21+TFH cells may prove to be a marker of OA disease activity.

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          The effects of specific medical conditions on the functional limitations of elders in the Framingham Study.

          The purpose of this study was to identify associations between specific medical conditions in the elderly and limitations in functional tasks; to compare risks of disability across medical conditions, controlling for age, sex, and comorbidity; and to determine the proportion of disability attributable to each condition. The subjects were 709 noninstitutionalized men and 1060 women of the Framingham Study cohort (mean age 73.7 +/- 6.3 years). Ten medical conditions were identified for study: knee osteoarthritis, hip fracture, diabetes, stroke, heart disease, intermittent claudication, congestive heart failure, chronic obstructive pulmonary disease, depressive symptomatology, and cognitive impairment. Adjusted odds ratios were calculated for dependence on human assistance in seven functional activities. Stroke was significantly associated with functional limitations in all seven tasks; depressive symptomatology and hip fracture were associated with limitations in five tasks; and knee osteoarthritis, heart disease, congestive heart failure, and chronic obstructive pulmonary disease, were associated with limitations in four tasks each. In general, stroke, depressive symptomatology, hip fracture, knee osteoarthritis, and heart disease account for more physical disability in noninstitutionalized elderly men and women than other diseases.
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            Increased Frequency of Circulating Follicular Helper T Cells in Patients with Rheumatoid Arthritis

            Follicular helper T (Tfh) cells are recognized as a distinct CD4+ helper T-cell subset, which provides for B-cell activation and production of specific antibody responses, and play a critical role in the development of autoimmune disease. So far, only one study investigated the circulating Tfh cells increased in a subset of SLE patients. Since relatively little is known about the Tfh cells in rheumatoid arthritis (RA) patients, in this study, Tfh-cell frequency, related cytokine IL-21, and transcription factor Bcl-6 were investigated in 53 patients with RA and 31 health controls. Firstly, we found that the frequency of CD4+CXCR5+ICOShigh Tfh cells was increased significantly in the peripheral blood of RA patients, compared with that in healthy controls. It is known that Tfh cells are critical for directing the development of an antibody response by germinal centers B cells; secondly, we observed that the Tfh-cell frequency is accompanied by the level of anti-CCP antibody in RA patients. Furthermore, expression of Bcl-6 mRNA and plasma IL-21 concentrations in RA patients was increased. Taken together, these findings have shown that the increased frequency of circulating Tfh cells is correlated with elevated levels of anti-CCP antibody, indicating the possible involvement of Tfh cells in the disease progression of RA.
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              High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis.

              This study aimed to examine the frequency of different subsets of circulating B and T follicular helper (Tfh) cells in patients with new-onset rheumatoid arthritis (RA) and following standard therapies. Twenty-five RA patients and 15 healthy controls (HC) were recruited for characterizing the frequency of CD27⁺, immunoglobulin (Ig)D⁺, CD86⁺, CD95⁺, Toll-like receptor (TLR)-9⁺ B cells and inducible T cell co-stimulator (ICOS) and programmed death 1 (PD-1)-positive Tfh cells and the level of serum interleukin (IL)-21. The potential correlation between the frequency of different subsets of B and Tfh cells and the values of clinical measures in RA patients was analysed. In comparison with HC, significantly higher percentages of circulating IgD⁺ CD27⁻ CD19⁺ naive B, CD86⁺ CD19⁺ and CD95⁺ CD19⁺ activated B, CD3⁺ CD4⁺ CXCR5⁺, CD3⁺ CD4⁺ CXCR5⁺ ICOS⁺, CD3⁺ CD4⁺ CXCR5⁺ PD-1⁺ and CD3⁺ CD4⁺ CXCR5⁺ ICOS⁺ PD-1⁺ Tfh cells but lower IgD⁺ CD27⁺ CD19⁺ preswitch memory B cells were detected, accompanied by significantly higher levels of serum IL-21 in the RA patients. Furthermore, the percentages of CD95⁺ B cells were correlated positively with the frequency of PD-1⁺ Tfh cells, but negatively with ICOS⁺ Tfh cells. The percentages of CD86⁺ B cells and ICOS⁺ Tfh cells were correlated positively with the values of disease activity score 28 (DAS28). Following the drug therapies for 1 month, the percentages of CD86⁺ B and PD-1⁺ Tfh cells were reduced significantly in the drug-responding patients. Our data suggest that activated B and Tfh cells may contribute to the pathogenesis of RA and the frequency of activated B and Tfh cells may be used as biomarkers for evaluating the therapeutic responses of individual patients with RA. © 2013 British Society for Immunology.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                March 2017
                19 January 2017
                19 January 2017
                : 15
                : 3
                : 1095-1102
                Affiliations
                [1 ]Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
                [2 ]Department of Orthopaedics, Shandong Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
                [3 ]Key Laboratory of Zoonosis Research, Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin 130032, P.R. China
                [4 ]Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, P.R. China
                Author notes
                Correspondence to: Professor Yanfang Jiang, Genetic Diagnosis Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, P.R. China, E-mail: yanfangjiang@ 123456hotmail.com
                Article
                mmr-15-03-1095
                10.3892/mmr.2017.6132
                5367351
                28112376
                281fa63e-eeec-4dac-9cdb-cab4759846dd
                Copyright: © Shan et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 20 November 2015
                : 18 November 2016
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                Articles

                follicular helper t cells,interleukin-21,osteoarthritis,western ontario and mcmaster universities osteoarthritis index

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