Prof. Dr. Ulrike Raap
Department of Dermatology and Allergy
University Hospital, Klinikum Oldenburg AöR
Faculty of Medicine and Health Sciences
University of Oldenburg

Dr. Barbara Horvath
Department of Dermatology
University of Groningen
University Medical Center Groningen

Dr. med. Nika Kotnik
PhD Student

Summary: Bullous Pemphigoid (BP) is one of the most common autoimmune diseases of the skin for which there is currently no cure. Early symptoms include urticarial erythema and severe itch, with tense blisters that occur in later stages of classical BP. Interestingly, there is a subgroup of patients without blisters which display erythematous-urticarial plaques as well as severe itch. The latter is known as non-bullous cutaneous pemphigoid; it is not readily diagnosed and the pathophysiology is poorly understood. Classical BP is characterized by a substantial accumulation of eosinophils in subepidermal blisters, skin lesions as well as blood eosinophilia. Additionally, skin lesions of classical BP contain increased numbers of basophils. In this study we aim to identify potential effector functions of eosinophil and basophil granulocytes in BP to discover what drives blister formation and the immunological differences between non-bullous and bullous cutaneous pemphigoid. We will focus on skin sections to investigate the accumulation, activation and signaling processes of eosinophil and basophil granulocytes to elucidate the mechanisms that regulate bullous and nonbullous cutaneous pemphigoid. Cytokine profiling and RNA sequencing will elucidate the complex mechanisms that govern the inflammatory processes in BP. In addition, transcriptome analysis and proteomic studies will unravel signaling pathways which regulate the activation of basophils and eosinophils. Finally, we will establish an ex vivo skin model for BP to reveal whether basophils drive the inflammation associated with BP. We hypothesize that basophils potentially play an important role in inducing the chemotaxis of eosinophils and their functional activation and thereby facilitate the development of blisters in BP. Our study will help us to understand the differential functional roles of eosinophils and basophils in bullous and non-bullous cutaneous pemphigoid in order to establish novel therapeutic treatment strategies against this debilitating disease of the elderly.

Publications:

• Infiltration analysis of eosinophils and basophils and co-expression of CD69, CD63, IL-31 and IgE in patients with bullous and non-bullous pemphigoid.

  Kotnik N, Langner A, Meyer NH, Pas HH, Gibbs BF, Meijer JM, Diercks GFH, Horváth B, Raap U.J Eur Acad Dermatol Venereol. 2024 Mar;38(3):e278-e281. doi: 10.1111/jdv.19593. Epub 2023 Nov 15.PMID: 37907267 No abstract available.

• IgE autoantibodies in serum and skin of non-bullous and bullous pemphigoid patients.

  Lamberts A, Kotnik N, Diercks GFH, Meijer JM, Di Zenzo G, Pas HH, Jonkman MF, Gibbs BF, Raap U, Horváth B.J Eur Acad Dermatol Venereol. 2021 Apr;35(4):973-980. doi: 10.1111/jdv.16996. Epub 2020 Nov 17.PMID: 33058320 Free PMC article.

• Expression of MicroRNA in Locoregional Recurrent Rectal Cancer.

  Kotnik N, El-Sourani N, Raap U, Raab HR, Bockhorn M, Meyer H, Troja A.Anticancer Res. 2020 May;40(5):2947-2953. doi: 10.21873/anticanres.14273.PMID: 32366447

• Neuronal branching of sensory neurons is associated with BDNF-positive eosinophils in atopic dermatitis.

  Guseva D, Rüdrich U, Kotnik N, Gehring M, Patsinakidis N, Agelopoulos K, Ständer S, Homey B, Kapp A, Gibbs BF, Ponimaskin E, Raap U.Clin Exp Allergy. 2020 May;50(5):577-584. doi: 10.1111/cea.13560. Epub 2020 Feb 4.PMID: 31925827

• Neurological disorders are associated with bullous pemphigoid.

  Papakonstantinou E, Limberg MM, Gehring M, Kotnik N, Kapp A, Gibbs BF, Raap U.J Eur Acad Dermatol Venereol. 2019 May;33(5):925-929. doi: 10.1111/jdv.15444. Epub 2019 Feb 27.PMID: 30663128

• Pemphigoid diseases as immune-related adverse effect following immune checkpoint inhibitors: A clinical case series of a diverse spectrum.

  Kotnik N, Diercks GFH, Jalving H, Hospers GAP, Oosting SF, van Kruchten M, Hiltermann TJN, Bolling MC, Bremer J, Horváth B, Meijer JM.JAAD Case Rep. 2025 Apr 4;61:100-106. doi: 10.1016/j.jdcr.2025.03.021. eCollection 2025 Jul.PMID: 40538786 Free PMC article. No abstract available.

• Gene Expression Profiling Suggests that Complement Activation Is Important for Blister Formation in Bullous Pemphigoid.

  Lamberts A, Kotnik N, Meijer JM, van Kempen LC, Diercks GFH, Horváth B.J Invest Dermatol. 2023 Aug;143(8):1591-1594.e2. doi: 10.1016/j.jid.2023.01.029. Epub 2023 Feb 28.PMID: 36863446 Free article. No abstract available.