Analysis of IL-10 and IL-35 in DPP-4 inhibitor-related bullous pemphigoid

The association between immunoregulatory cytokines, such as IL-10 or IL-35, and DPP-4 inhibitor-related bullous pemphigoid (BP) has not been evaluated. Sera were collected from 39 Japanese patients with BP (24 males and 15 females; 77.0 ± 11.1 years old) including 6 patients with non-DPP-4 inhibitor-related BP before treatment in our hospital. Ten healthy Japanese individuals (4 males and 6 females; 42.2 ± 9.37 years old) were enrolled as healthy controls. No significant difference was observed in serum IL-10 levels (BP patients: 7.63 ± 5.03 pg/ml; healthy individuals: 6.88 ± 0.52 pg/ml; DPP-4 inhibitor-related BP: 6.77 ± 0.24 pg/ml; non-DPP-4 inhibitor-related BP: 6.84 ± 0.20 pg/ml; BP vs healthy: P  = 0.368; DPP-4 inhibitor-related BP vs non-DPP-4 inhibitor-related BP: P  = 0.553), nor in serum IL-35 levels (BP patients: 2.62 ± 0.20 pg/ml; healthy individuals: 2.60 ± 0.17 pg/ml; DPP-4 inhibitor-related BP: 2.63 ± 0.17 pg/ml; non-DPP-4 inhibitor-related BP: 2.63 ± 0.21 pg/ml; BP vs healthy: P  = 0.727; DPP-4 inhibitor-related BP vs non-DPP-4 inhibitor-related BP: P  = 0.949). Bullous Pemphigoid Disease Area Index (BPDAI) before treatment was not related with serum IL-10 levels (r = 0.159; Fig. 1A), nor with serum IL-35 levels (r = 0.227; Fig. 1B). The number of serum eosinophils was significantly higher in patients with non-DPP-4 inhibitor-related BP (911.3 ± 948.8) than in patients with DPP-4 inhibitor-related BP (476.1 ± 234.0; P  = 0.038). DPP-4 is also known as a CD26 molecule expressed on the surface of T lymphocytes. The mean rate of infiltrating CD26 + cells was significantly increased in 6 patients with DPP-4 inhibitor-related BP (32.9 ± 7.1) than in 6 patients with non-DPP-4 inhibitor-related BP (15.7 ± 4.4; P  = 0.002; Fig. 2). It was reported that the co-engagement of CD3 and CD26 induces the preferential production of IL-10 from human CD4 + T cells, which might reflect the clinical characteristics of faint inflammatory bulla in DPP-4 inhibitor-related BP.