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      Cut-off values for IL-21 and IL-23 as biochemical markers for pemphigus vulgaris

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          Abstract

          Pemphigus vulgaris (PV) is a potentially fatal mucocutaneous autoimmune disease characterized by severe skin lesions. Interleukin-21 (IL-21) and IL-23 have been linked to several autoimmune inflammatory diseases that may have a critical role in PV immunopathogenesis, including T-helper 17 (Th17) development. This study aimed to compare the serum levels of IL-21 and IL-23 in patients with PV and healthy controls. This case-control study included 90 participants (45 patients and 45 controls). Serum IL-21 and IL-23 were measured using the Sandwich-ELISA method provided by Sunlong Biotech, China. The findings revealed statistically significant results for IL-21 O.D. and Conc. (p=0.012*) and highly significant results for IL-23 O.D. and Conc. (p=0.000**). Furthermore, cut-off values were established for IL-21 (O.D.=0.071 pg/mL, Conc.=6.468 pg/mL) and IL-23 (O.D.=0.141 pg/mL, Conc.=6.745 pg/mL). These results indicate a potential association between PV and IL-21, IL-23, and the identified cut-off values. The particular roles of cytokines and how they can be utilized to treat PV require more investigation. To our knowledge, this was the first study to detect a cut-off point for IL-21 and IL-23 that may be used as novel and cost-effective biochemical markers for disease diagnosis.

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          Receiver Operating Characteristic (ROC) Curve Analysis for Medical Diagnostic Test Evaluation.

          This review provides the basic principle and rational for ROC analysis of rating and continuous diagnostic test results versus a gold standard. Derived indexes of accuracy, in particular area under the curve (AUC) has a meaningful interpretation for disease classification from healthy subjects. The methods of estimate of AUC and its testing in single diagnostic test and also comparative studies, the advantage of ROC curve to determine the optimal cut off values and the issues of bias and confounding have been discussed.
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            Pemphigus: Current and Future Therapeutic Strategies

            Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.
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              Clinical significance and immunobiology of IL-21 in autoimmunity

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                Author and article information

                Contributors
                Journal
                J Med Life
                J Med Life
                JMedLife
                Journal of Medicine and Life
                Carol Davila University Press (Romania )
                1844-122X
                1844-3117
                September 2023
                : 16
                : 9
                : 1407-1414
                Affiliations
                [1 ]Department of Oral Medicine, College of Dentistry, University of Baghdad, Baghdad, Iraq
                [2 ]Department of Oral Diagnosis, College of Dentistry, University of Baghdad, Baghdad, Iraq
                Author notes
                [* ] Corresponding Author: Zahra Ali Al-Hasnawi Department of Oral Medicine, College of Dentistry, University of Baghdad, Baghdad, Iraq E-mail: zahra_alhassnawi@ 123456yahoo.com
                Article
                JMedLife-16-1407
                10.25122/jml-2023-0226
                10719779
                38107713
                9bb74018-7dd1-4cbf-aa05-689993b4459b
                ©2023 JOURNAL of MEDICINE and LIFE

                This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0

                History
                : 13 July 2023
                : 20 August 2023
                Categories
                Original Article

                Medicine
                pemphigus vulgaris,il-21,il-23,cuttoff point
                Medicine
                pemphigus vulgaris, il-21, il-23, cuttoff point

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