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      Serum chemerin levels: A potential biomarker of joint inflammation in women with rheumatoid arthritis

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          Abstract

          Background

          Chemerin has a potential role in perpetuating inflammation in autoimmune diseases. Nevertheless, to date, there is no conclusive information on whether high chemerin levels increase the severity of rheumatoid arthritis (RA). Therefore, this study evaluated whether serum chemerin is a biomarker of disease activity in RA patients.

          Methods

          Study design: cross-sectional. The assessment included clinical and laboratory characteristics, body mass index (BMI) and fat mass. The severity of the disease activity was identified according to the DAS28-CRP index as follows: A) RA with a DAS28-CRP≤2.9 (remission/mild activity) and B) RA with a DAS28-CRP>2.9 (moderate/severe activity). Serum chemerin concentrations were measured by ELISA, and ≥103 ng/mL was considered a high level. Logistic regression analysis was applied to determine whether high chemerin levels were associated with disease activity in RA after adjusting for confounders. Multiple regression analysis was performed to identify variables associated with chemerin levels.

          Results

          Of 210 RA patients, 89 (42%) subjects had moderate/severe disease activity and had higher serum chemerin levels than patients with low disease activity or remission (86 ± 34 vs 73± 27; p = 0.003). Serum chemerin correlated with the number of swollen joints (r = 0.15; p = 0.03), DAS28-CRP (r = 0.22; p = 0.002), and C-reactive protein levels (r = 0.14; p = 0.04), but no correlation was observed with BMI and fat mass. In the adjusted logistic regression analysis, high chemerin levels (≥103 ng/mL) were associated with an increased risk of moderate/severe disease activity (OR: 2.76, 95% CI 1.35–5.62; p = 0.005). In the multiple regression analysis, after adjusting for potential confounders, serum chemerin levels were associated with higher DAS28-CRP (p = 0.002).

          Conclusions

          Higher chemerin levels increased the risk of moderate and severe disease activity in RA. These results support the role of chemerin as a marker of inflammation in RA. Follow-up studies will identify if maintaining low chemerin levels can be used as a therapeutic target.

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          Most cited references33

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          2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

          The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."
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            The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis

            The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.
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              Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis

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                Author and article information

                Contributors
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 September 2021
                2021
                : 16
                : 9
                : e0255854
                Affiliations
                [1 ] Departamento de Fisiología Centro Universitario de Ciencias de la Salud, Programa de Doctorado en Farmacología, Instituto de Terapeutica Experimental y Clínica, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
                [2 ] Departamento de Salud Pública, Programa de Doctorado en Salud Publica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
                [3 ] Unidad de Investigación Biomédica 02, Hospital de Especialidades, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
                [4 ] Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
                [5 ] Servicio de Epidemiología, Unidad de Medicina Familiar número 04, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México
                [6 ] Unidad Medica Familiar 97, Instituto Mexicano del Seguro Social, Magdalena, Jalisco, México
                [7 ] Centro Universitario de Investigaciones Biomedicas, Universidad de Colima, Colima, Mexico
                [8 ] División de Ciencias de la Salud, Departamento de Ciencias Biomédicas, Departamento Salud-Enfermedad como Proceso Individual, Centro Universitario de Tonalá, Universidad de Guadalajara, Tonalá, Jalisco México
                [9 ] Departamento de Microbiologia y Patologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
                [10 ] Departamento de Medicina Interna-Reumatología, Hospital General Regional 110, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
                Nippon Medical School, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ FGP and JIGN participated equally in this work and should be considered as co-first authors.

                ¶ Membership of the Research Group for the Assessment of Prognosis Biomarkers in Autoimmune Disorders can be found in the Acknowledgments.

                Author information
                https://orcid.org/0000-0001-7506-1674
                https://orcid.org/0000-0002-6517-6344
                Article
                PONE-D-21-15276
                10.1371/journal.pone.0255854
                8432803
                34506500
                6d5e0281-f691-4db0-b488-a146fb272f17
                © 2021 Gonzalez-Ponce et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 May 2021
                : 24 July 2021
                Page count
                Figures: 2, Tables: 3, Pages: 13
                Funding
                The author(s) received no specific funding for this work.
                Categories
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                Medicine and Health Sciences
                Rheumatology
                Arthritis
                Rheumatoid Arthritis
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Autoimmune Diseases
                Rheumatoid Arthritis
                Biology and Life Sciences
                Immunology
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