Lim Yen Loo, Bohelay Gerome, Hanakawa Sho, Musette Philippe, Janela Baptiste
Department of Dermatology, National Skin Centre, Singapore.
Department of Dermatology and INSERM U1125, Avicenne Hospital, Bobigny, France.
Front Mol Biosci. 2022 Feb 4;8:808536. doi: 10.3389/fmolb.2021.808536. eCollection 2021.
Pemphigus represents a group of rare and severe autoimmune intra-epidermal blistering diseases affecting the skin and mucous membranes. These painful and debilitating diseases are driven by the production of autoantibodies that are mainly directed against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1). The search to define underlying triggers for anti-Dsg-antibody production has revealed genetic, environmental, and possible vaccine-driven factors, but our knowledge of the processes underlying disease initiation and pathology remains incomplete. Recent studies point to an important role of T cells in supporting auto-antibody production; yet the involvement of the myeloid compartment remains unexplored. Clinical management of pemphigus is beginning to move away from broad-spectrum immunosuppression and towards B-cell-targeted therapies, which reduce many patients' symptoms but can have significant side effects. Here, we review the latest developments in our understanding of the predisposing factors/conditions of pemphigus, the underlying pathogenic mechanisms, and new and emerging therapies to treat these devastating diseases.
天疱疮是一组罕见且严重的自身免疫性表皮内水疱性疾病，累及皮肤和黏膜。这些疼痛且使人衰弱的疾病是由主要针对桥粒黏附蛋白桥粒芯糖蛋白3（Dsg3）和桥粒芯糖蛋白1（Dsg1）的自身抗体产生所驱动。对确定抗Dsg抗体产生的潜在触发因素的研究揭示了遗传、环境以及可能由疫苗驱动的因素，但我们对疾病起始和病理过程的了解仍不完整。最近的研究指出T细胞在支持自身抗体产生中起重要作用；然而髓系细胞区室的参与情况仍未得到探索。天疱疮的临床管理正开始从广谱免疫抑制转向以B细胞为靶点的疗法，这些疗法减轻了许多患者的症状，但可能有显著的副作用。在此，我们综述了在天疱疮的易感因素/条件、潜在致病机制以及治疗这些毁灭性疾病的新出现疗法方面我们理解的最新进展。
