Clinical and immunological impact of booster immunization with recombinant mRNA vaccines for SARS-CoV-2 in patients with pemphigus and bullous pemphigoidDear Editor, There is scepticism toward mRNA vaccines due to the growing number of reports linking SARS-CoV-2 mRNA vaccinations with the onset or relapse of inflammatory/autoimmune diseases such as pemphigus and bullous pemphigoid (BP). 1,2 However, there is a lack of immunological studies assessing the safety of these vaccines in these patient cohorts, since phase 3 studies with BNT162b2 or mRNA-1273 did not include patients with autoimmune or inflammatory disorders. 3,4 Clinical observation from daily practice shows that although some individuals may experience disease onset or relapse, most patients with pemphigus or BP who receive mRNA-based SARS-CoV-2 vaccines do not experience disease flares. 5 Prospective clinical and immunological data for these two patient populations on safety and efficacy of mRNA-based SARS-CoV-2 booster vaccinations are scarce. We followed clinical and immunological parameters in patients with pemphigus (n = 9), BP (n = 4) and healthy individuals (HI) up to 4 weeks after booster immunization with either BNT162b2 or mRNA-1273. Table 1 summarizes the patients' characteristics. Cytofluorimetric analysis revealed an increase in T helper (Th) 1 and Th17.1 cells in patients with pemphigus at 4 weeks after booster vaccination, whereas Th17 cells concomitantly decreased. Th2 cells showed no significant changes
Studies on the role of interleukins (ILs) in autoimmune and inflammatory diseases allow for the better understanding of pathologic mechanisms of disease and reshaping of treatment modalities. The development of monoclonal antibodies targeting specific ILs or IL signaling pathways (i.e., anti‐IL‐17/IL‐23 in psoriasis or anti‐IL‐4/IL‐13 in atopic dermatitis) is the shining example of therapeutic interventions in research. IL‐21, belonging to the group of ɣc‐cytokines (IL‐2, IL‐4, IL‐7, IL‐9, and IL‐15), is gaining attention for its pleiotropic role in several types of immune cells as activator of various inflammatory pathways. In both health and disease, IL‐21 sustains T‐ and B‐cell activity. Together with IL‐6, IL‐21 helps to generate Th17 cells, promotes CXCR5 expression in T cells, and their maturation into follicular T helper cells. In B cells, IL‐21 sustains their proliferation and maturation into plasma cells and promotes class switching and antigen‐specific antibody production. Due to these characteristics, IL‐21 is a main factor in numerous immunologic disorders, such as rheumatoid arthritis and MS. Studies in preclinical skin disease models and on human skin strongly suggest that IL‐21 is crucially involved in inflammatory and autoimmune cutaneous disorders. Here, we summarize the current knowledge of IL‐21 in well‐known skin diseases.
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