Dipeptidylpeptidase-4 inhibitor-associated bullous pemphigoid is characterized by an altered expression of cytokines in the skin.

Dipeptidyl peptidase 4 inhibitors (DPP4i), 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 (rBP) are largely unknown. We analyzed the expression of 32 cytokines and two proteases by Luminex and ELISA assays in samples taken from lesional and non-lesional skin of patients with rBP or DPP4i-BP, and healthy controls. Cytokines mediating B-cell survival and targeting such as B-cell activating factor (BAFF), CC chemokine ligand (CCL) 4, CXC chemokine ligand (CXCL) 12 and interleukin (IL) -6 were expressed at a higher level in the lesional rBP skin compared to that of DPP4i-BP. 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, IL-6, CCL1, CCL17, CCL26 and IL-5 measured by quantitative polymerase chain reaction correlated with the protein levels. Taken together, the cutaneous cytokine profiles were found to provide distinctive molecular fingerprints between rBP and DPP4i-BP.