Divergent in situ expression of IL‐31 and IL‐31RA between bullous pemphigoid and pemphigus vulgaris

Author:

Ergun Ecem Zeliha12ORCID,Aoki Rui1ORCID,Horváth Orsolya N.1,Hartmann Daniela1ORCID,Satoh Takashi K.1ORCID,Calabrese Laura134ORCID,Aksu Ayşe Esra Koku5,Gürel Mehmet Salih6,Manav Vildan5,Flaig Michael J.1,Sárdy Miklós17ORCID,Ruzicka Thomas1,French Lars E.18ORCID,Bağcı Işın Sinem9ORCID

Affiliation:

1. Department of Dermatology and Allergy University Hospital of Munich, Ludwig‐Maximilian‐University (LMU) Munich Germany

2. Department of Dermatology, Haydarpaşa Training and Research Hospital Health Science University Istanbul Turkey

3. Institute of Dermatology Catholic University of the Sacred Heart Rome Italy

4. Dermatology Unit, Department of Medical, Surgical and Neurological Sciences University of Siena Siena Italy

5. Department of Dermatology, Istanbul Training and Research Hospital Health Science University Istanbul Turkey

6. Department of Dermatology and Venereology, Göztepe Prof. Dr Süleyman Yalçın City Hospital Istanbul Medeniyet University Istanbul Turkey

7. Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine Semmelweis University Budapest Hungary

8. Dr. Phillip Frost, Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami Florida USA

9. Department of Dermatology Stanford University, School of Medicine California USA

Abstract

AbstractBullous pemphigoid (BP) and pemphigus vulgaris (PV) are two major autoimmune blistering skin diseases. Unlike PV, BP is accompanied by intense pruritus, suggesting possible involvement of the pruritogenic cytokine IL‐31. However, the underlying mechanisms of the clinical difference between BP and PV in terms of pruritus are not fully understood. To compare the expression levels of IL‐31 and its receptor IL‐31RA in the lesional skin, including peripheral nerves in BP and PV patients, immunohistochemical staining for IL‐31 and IL‐31RA was performed in skin samples of BP and PV patients and healthy controls (HC). The IL‐31RA‐expressing area in epidermis and peripheral nerves was analysed using ImageJ and the percentage of positive cells for IL‐31/IL‐31RA in dermal infiltrating cells was manually quantified. Quantitative analyses revealed that IL‐31/IL‐31RA expressions in the epidermis and dermal infiltrate were significantly increased in BP compared to PV and HC. The difference between BP and PV became more obvious when advanced bullous lesions were compared. Peripheral nerves in BP lesions presented significantly higher IL‐31RA expression compared to PV lesions. In conclusion, we found significantly augmented expressions of IL‐31/IL‐31RA in BP lesions, including peripheral nerves, in comparison to PV. These results suggest a possible contribution of IL‐31/IL‐31RA signalling to the difference between BP and PV in the facilitation of pruritus and local skin inflammation, raising the possibility of therapeutic targeting of the IL‐31/IL‐31RA pathway in BP patients.

Publisher

Wiley

Subject

Dermatology,Molecular Biology,Biochemistry

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