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This article discusses the differences between checkpoint inhibitor-induced bullous pemphigoid (irBP) and spontaneous bullous pemphigoid (BP). The study compared patients with irBP to patients with BP and found that irBP patients were younger, had a shorter duration of disease, and had a better therapeutic response. However, irBP patients required permanent discontinuation of ICI therapy in 78% of cases. The article provides clinical characteristics and treatment information for both irBP and BP patients. The study also identified differentially expressed genes in irBP compared to BP and normal skin tissue, suggesting potential targets for irBP treatment. The JAK-STAT signaling pathway was found to be enriched in both irBP and BP, indicating that JAK inhibitors could be potential treatment options. The study was funded by grants and the authors declare potential conflicts of interest. [Extracted from the article]

A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced. Those mechanisms of action include a broad therapeutic spectrum of substances targeting various protein kinases, some of which could also be used for the treatment of other autoimmune-mediated diseases. The advancement of new compounds could therefore enable a more personalized approach in treating MS, taking into consideration patients' co-existing autoimmune-mediated diseases. In this review, we discuss potential compounds targeting protein kinases, currently under investigation in clinical trials for various autoimmune diseases that could become viable treatment options for MS and comorbid autoimmune conditions in the future., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest. MW, SL, KH, PS and DH have not received travel grants or honoraria. FFK received travel grants from Merck and Novartis and is a Hannover Medical School- and German Research Foundation (DFG)–funded fellow as part of the Clinician Scientist Program (PRACTIS) at Hannover Medical School. NM received travel grants and honoraria for lecturing from Biogen, Merck, and Novartis. TW received honoraria as speaker from Roche and Novartis. MS received honoraria as speaker and for consultation from Almirall and AbbVie. KFJ received research support from Else Kröner Fresenius Foundation and travel compensation and congress fee from Merck and Novartis. SG reports research support from Alnylam Pharmaceuticals, CSL Behring, Else Kröner Fresenius Foundation, Deutsche Forschungsgemeinschaft and Hannover Biomedical Research School (HBRS) and consulting and/or speaker honoraria from Alexion, Alnylam Pharmaceuticals, AstraZeneca, GSK, Pfizer and Merck all outside the submitted work. KWS reports honoraria for lectures or travel reimbursements for attending meetings from Biogen, Merck, Bavarian Nordic and Bristol-Myers Squibb as well as research support from Bristol-Myers Squibb. MAF received honoraria as speaker and for consultation from Alexion, Biogen, Lundbeck, Merck KGaA, Novartis, Roche and Sudo Biosciences. His research is funded by the Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Landesforschungsförderung Hamburg, Gemeinnützige Hertie-Stiftung, Else Kröner-Fresenius-Stiftung, Deutsche Multiple Sklerose-Gesellschaft, Fritz Thyssen-Stiftung, Werner Otto-Stiftung, Walter und Ilse Rose-Stiftung, Stiftung zur Bekämpfung neuroviraler Erkrankungen and Research Fund of the University Medical Center Hamburg-Eppendorf. LK received compensation for serving on Scientific Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Genzyme, Horizon, Janssen, Merck Serono, Novartis, Roche and Viatris. She received speaker honoraria and travel support from Argenx, Bayer, Biogen, Bristol-Myers Squibb, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera and Teva. She receives research support from the German Research Foundation, the IZKF Münster, IMF Münster, Biogen, Immunic AG, Novartis and Merck Serono. RP received honoraria for lecturing and travel expenses from Biogen, Bristol-Myers Squibb, Horizon, Janssen Pharmaceuticals, Merck Serono, Novartis, Roche, and Sanofi-Aventis. His research is funded by Merck Serono and Novartis. MP received honoraria for lecturing and travel expenses for attending meetings from Alexion, ArgenX, Bayer Health Care, Biogen, Hexal, Merck Serono, Novartis, Roche, Sanofi-Aventis, Takeda and Teva. His research is funded by ArgenX, Biogen, Demecan, Hexal, Horizon Merck Serono, Novartis, Roche, Viatris, Takeda and Teva. CK received honoraria for lecturing and travel expenses for attending meetings from Alexion, Almirall, Astra Zenica, Bayer, Biogen, Biontech, Boehringer Ingelheim Bristol Myers-Squibb, C.T.I., Daiichi Sankyo, Docspert, Merck Serono, Mylan/Viatris, Novartis, Pfizer, Roche, Sanofi-Aventis, Stada, Teva, Janssen-Cilag, Horizon Therapeutics, Medscape LLC, Baumgart Consultants, StreamedUp!, Hexal/Sandoz, Agentur Süss, Viatris. SGM received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Bundesinstitut für Risikobewertung (BfR), Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, Gemeinsamer Bundesausschuss (G-BA), German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and by Alexion, Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. TS reports research support from Alnylam Pharmaceuticals, CSL Behring, Novartis, Siemens; honoraria for lectures and travel expenses for attending meetings from Alexion, Alnylam Pharmaceuticals, argenx, Bayer Vital, Biogen, Bristol Myers Squibb, Celgene, Centogene, CSL Behring, Euroimmun, Grifols, Hexal AG, Horizon, Janssen-Cilag, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Swedish Orphan Biovitrum, Teva, Viatris; consultant fees from Alexion, Alnylam Pharmaceuticals, Biogen, Centogene, CSL Behring, Grifols, Hexal AG, Janssen-Cilag, Merck Serono, Novartis, Roche, Sanofi, Swedish Orphan Biovitrum, Viatris., (Copyright © 2025. Published by Elsevier B.V.)

Objective: Systemic sclerosis (SSc) is a severe rheumatic disease causing fibrotic tissue rearrangement. Aberrant toll-like receptor (TLR) 8 transcripts in plasmacytoid dendritic cells (pDCs) were recently linked to SSc pathogenesis, which is at least partially mediated by increased type I interferon (IFN-I) responses. Here, we addressed the functional role of TLR8 signaling in different immune cell subsets of patients with SSc., Methods: Monocytes, conventional dendritic cells (cDCs), and pDCs from the blood and skin of patients with SSc were analyzed for TLR8 protein expression. To assess TLR function, cytokine responses upon TLR7 and TLR8 stimulation were studied. To identify relevant alterations specific for patients with SSc (n = 16), patients with primary Sjögren disease (pSS; n = 10) and healthy controls (HCs; n = 13) were included into the study., Results: In all individuals, TLR8 was expressed in monocytes and cDCs but not in pDCs. The TLR8 expression levels were overall similar in patients with SSc and pSS and HCs. Additionally, in all study participants, TLR8 stimulation of pDCs did not induce IFN-I expression. In contrast, monocytes from patients with SSc revealed increased interleukin (IL)-10 responses upon TLR8 (patients with SSc vs HCs, P = 0.0126) and TLR7/8 stimulation (patients with SSc vs HCs, P = 0.0170)., Conclusion: TLR8 protein is not expressed in pDCs of patients with SSc. Accordingly, they do not respond to TLR8 stimulation. In contrast, monocytes of patients with SSc respond to TLR8 stimulation with increased IL-10 responses. Therefore, TLR8 signaling in monocytes participates in SSc pathogenesis by conferring aberrant IL-10 expression., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

More than 10 disease-modifying therapies (DMT) are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS) and new therapeutic options are on the horizon. Due to different underlying therapeutic mechanisms, a more individualized selection of DMTs in MS is possible, taking into account the patient's current situation. Therefore, concomitant treatment of various comorbid conditions, including autoimmune mediated disorders such as rheumatoid arthritis, should be considered in MS patients. Because the pathomechanisms of autoimmunity partially overlap, DMT could also treat concomitant inflammatory diseases and simplify the patient's treatment. In contrast, the exacerbation and even new occurrence of several autoimmune diseases have been reported as a result of immunomodulatory treatment of MS. To simplify treatment and avoid disease exacerbation, knowledge of the beneficial and adverse effects of DMT in other autoimmune disorders is critical. Therefore, we conducted a literature search and described the beneficial and adverse effects of approved and currently studied DMT in a large number of comorbid autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, cutaneous disorders including psoriasis, Sjögren´s syndrome, systemic lupus erythematosus, systemic vasculitis, autoimmune hepatitis, and ocular autoimmune disorders. Our review aims to facilitate the selection of an appropriate DMT in patients with MS and comorbid autoimmune diseases., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest. FFK received travel grants from Merck and Novartis. NM received honoraria for scientific lectures from Novartis, Merck, and Biogen. TW received honoraria as speaker from Roche and Novartis. MS received honoraria as speaker and for consultation from Almirall and AbbVie. KWS reports honoraria for lectures or travel reimbursements for attending meetings from Biogen, Merck, Bavarian Nordic and Bristol-Myers Squibb as well as research support from Bristol-Myers Squibb. MAF received honoraria as speaker and for consultation from Biogen, Lundbeck, Merck KGaA, Novartis and Roche. His research is funded by the Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Landesforschungsförderung Hamburg, Gemeinnützige Hertie-Stiftung, Else Kröner-Fresenius-Stiftung, Deutsche Multiple Sklerose-Gesellschaft, Fritz Thyssen-Stiftung, Werner Otto-Stiftung, Walter und Ilse Rose-Stiftung, Stiftung zur Bekämpfung neuroviraler Erkrankungen and Research Fund of the University Medical Center Hamburg-Eppendorf. LK received compensation for serving on Scientific Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Genzyme, Horizon, Janssen, Merck Serono, Novartis, Roche and Viatris. She received speaker honoraria and travel support from Argenx, Bayer, Biogen, Bristol-Myers Squibb, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera and Teva. She receives research support from the German Research Foundation, the IZKF Münster, IMF Münster, Biogen, Immunic AG, Novartis and Merck Serono. RP received honoraria for lecturing and consulting from Alexion, Bayer Healthcare, Biogen, Bristol-Mayers Squibb, MedDay, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme. He received research funds from Teva, Merck Serono, and Novartis. MP received honoraria for lecturing from Argenx, Biogen, Bayer, Novartis, Hexal, Sanofi and Merck. He received research funding from Novartis and Biogen. His research is funded by the German Multiple Sclerosis Society North Rhine-Westphalia (DMSG). CK received honoraria for lecturing and consulting as well as financial research support from Ablynx, Almirall, Amgen, Bayer Vital, Bristol-Mayers Squibb, Biotronik, Boehringer Ingelheim, Biogen, CSL Behring, Daiichi-Sankyo, Desitin, Eisai, Ever Pharma, Sanofi Genzyme, Merck Serono, Mylan, Medday, Novartis, Pfizer, Roche, Siemens, Stago, and Teva. SGM received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Bundesinstitut für Risikobewertung (BfR), Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, Gemeinsamer Bundesausschuss (G-BA), German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and by Alexion, Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. TS reports honoraria for lectures and travel grants from Alexion, Alnylam Pharmaceuticals, argenx, Bayer Vital, Biogen, Celgene, Centogene, CSL Behring, Euroimmun, Janssen, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Sobi, Teva. His research is supported by the German Ministry for Education and Research (BMBF), Bristol-Myers Squibb Foundation for Immuno-Oncology, Claudia von Schilling Foundation for Breast Cancer Research, Else Kröner Fresenius Foundation, Hannover Biomedical Research School (HBRS), Alnylam Pharmaceuticals, CSL Behring, Novartis, Sanofi Genzyme, VHV Stiftung., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15-/- dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. ISG15-/- fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15-/- fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15-/- 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-β1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets.

Competing Interests: None disclosed.

Competing Interests: Die Autoren geben an, dass kein Interessenskonflikt besteht.