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      Targeting therapy in pemphigus: Where are we now and where are we going?

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          Abstract

          Pemphigus is a heterogeneous group of autoimmune skin disorders characterized by blistering of the skin and mucosal membranes, potentially affecting the quality of life if left unchecked. The current mainstay of treatment is systemic corticosteroids and immunosuppressive agents. Nevertheless, long-term use of these drugs can easily cause infections and other life-threatening adverse reactions. Thus, currently, researchers are trying to develop new and safer therapeutic approaches. Specifically, targeted therapies to pathogenic immune pathways have been gradually introduced and used for the treatment of pemphigus or in clinical trials, such as monoclonal anti-CD20 antibody, BAFF inhibitor, BTK inhibitor, CAAR-T therapy, FcRn antagonist, and TNF-α inhibitor. In addition, IL-4Rα antibody, IL-17 blockade, mTOR pathway inhibitor, CTLA-4Ig, and p38 MAPK inhibitors are theoretically promising treatment for pemphigus. Here, we review the research progress on the mechanism of targeted therapies for pemphigus.

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          Most cited references68

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          Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

          Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3 ζ signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease.
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            B cell depletion therapies in autoimmune disease: advances and mechanistic insights

            In the past 15 years, B cells have been rediscovered to be not merely bystanders but rather active participants in autoimmune aetiology. This has been fuelled in part by the clinical success of B cell depletion therapies (BCDTs). Originally conceived as a method of eliminating cancerous B cells, BCDTs such as those targeting CD20, CD19 and BAFF are now used to treat autoimmune diseases, including systemic lupus erythematosus and multiple sclerosis. The use of BCDTs in autoimmune disease has led to some surprises. For example, although antibody-secreting plasma cells are thought to have a negative pathogenic role in autoimmune disease, BCDT, even when it controls the disease, has limited impact on these cells and on antibody levels. In this Review, we update our understanding of B cell biology, review the results of clinical trials using BCDT in autoimmune indications, discuss hypotheses for the mechanism of action of BCDT and speculate on evolving strategies for targeting B cells beyond depletion.
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              First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.

              High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                25 May 2023
                June 2023
                25 May 2023
                : 9
                : 6
                : e16679
                Affiliations
                [1]Department of Dermatology and Venereology, People's Hospital of Xinjiang Uygur Autonomous Region; Xinjiang Clinical Research Center for Dermatologic Diseases; Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi 830002, China
                Author notes
                []Corresponding author. drliangjq@ 123456163.com
                [1]

                Kailibinuer Abulikemu and Fengxia Hu contributed equally to this work and should be considered co-first authors.

                [2]

                Junqin Liang and Xiaojing Kang contributed equally to this work and should be considered co-corresponding authors.

                Article
                S2405-8440(23)03886-0 e16679
                10.1016/j.heliyon.2023.e16679
                10245244
                37292301
                bbc7d650-0ced-419b-b1cb-2e36c4389a7a
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 4 September 2022
                : 24 May 2023
                : 24 May 2023
                Categories
                Review Article

                pemphigus,treatment,target therapy,biological therapy,rituximab

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