University of Oulu

Tuusa, J., Kokkonen, N., Mattila, A., Huilaja, L., Varpuluoma, O., Rannikko, S., Glumoff, V., Miettunen, J., & Tasanen, K. (2023). Dipeptidyl Peptidase 4 Inhibitor‒Associated Bullous Pemphigoid Is Characterized by an Altered Expression of Cytokines in the Skin. In Journal of Investigative Dermatology (Vol. 143, Issue 1, pp. 78-86.e12). Elsevier BV.

Dipeptidyl peptidase 4 inhibitor‒associated bullous pemphigoid Is characterized by an altered expression of cytokines in the skin

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Author: Tuusa, Jussi1,2,3; Kokkonen, Nina1,2,3; Mattila, Anja1,2,3;
Organizations: 1PEDEGO Research Unit, University of Oulu, Oulu, Finland
2Department of Dermatology, Oulu University Hospital, Oulu, Finland
3Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
4Research Unit of Biomedicine and Medical Research Center, Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland
5Center for Life Course Health Research, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3 MB)
Persistent link:
Language: English
Published: Elsevier, 2022
Publish Date: 2023-09-29


Dipeptidyl peptidase 4 inhibitors (DPP4is), commonly used drugs for treatment of type 2 diabetes, increase the risk for bullous pemphigoid (BP). Currently, the mechanism leading to the loss of immunological tolerance of the cutaneous adhesion molecule BP180 as well as similarities and differences in disease progression between DPP4i-associated BP (DPP4i-BP) and DPP4i-independent regular BP are largely unknown. We analyzed the expression of 32 cytokines and two proteases by Luminex and ELISA assays in samples taken from lesional and nonlesional skin of patients with regular BP or DPP4i-BP and healthy controls. Cytokines mediating B-cell survival and targeting such as BAFF, CCL4, CXCL12, and IL-6 were expressed at a higher level in the lesional regular BP skin than the levels in the lesional DPP4i-BP skin. The DPP4i-BP samples had increased levels of eosinophilic cytokines CCL1, CCL17, CCL26, and IL-5, which correlated with the serum level of anti-BP180 NC16A IgG autoantibodies. The mRNA expression of BAFF, IL6, CCL1, CCL17, CCL26, and IL5 measured by qPCR correlated with the protein levels. Taken together, the cutaneous cytokine profiles were found to provide distinctive molecular fingerprints between regular BP and DPP4i-BP.

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Series: Journal of investigative dermatology
ISSN: 0022-202X
ISSN-E: 1523-1747
ISSN-L: 0022-202X
Volume: 143
Issue: 1
Pages: 78 - 86.e12
DOI: 10.1016/j.jid.2022.07.006
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This study was financially supported by grants from the Academy of Finland, Finland (grant number 294738); the Sigrid Juselius Foundation; and the Medical Research Center, Oulu University Hospital.
Academy of Finland Grant Number: 294738
Detailed Information: 294738 (Academy of Finland Funding decision)
Dataset Reference: No extra datasets on top of those shown in this study were generated during this study.
Copyright information: © 2022 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This is an open access article under the CC BY license (