A Cross-Sectional Study Comparing the Prevalence of Bullous Pemphigoid Autoantibodies in 275 Cases of Type II Diabetes Mellitus Treated With or Without Dipeptidyl Peptidase-IV Inhibitors

Front Immunol. 2019 Jun 26;10:1439. doi: 10.3389/fimmu.2019.01439. eCollection 2019.


Background: Anti-hyperglycemic drug dipeptidyl peptidase-IV inhibitors (DPP-4i) have recently been recognized as bullous pemphigoid (BP) inducing drugs. It remains uncertain whether DPP-4i induce BP-IgG autoantibodies before the onset of BP. Objective: To evaluate the effect of DPP-4i in the development of BP-IgG autoantibodies in type 2 diabetes mellitus (T2DM) patients. Methods: A cross-sectional study on 221 DPP-4i (+) and 54 DPP-4i (-) T2DM cases was conducted. BP180 NC16A, BP230, and full-length BP180 ELISAs were used to detect the BP-IgG autoantibodies. We have also statistically analyzed the proportion of age, gender, intake periods of DPP-4i, and hemoglobin A1c level between anti-full-length BP180 IgG-positive and -negative DPP-4i (+) T2DM cases to identify co-founding factors. Results: BP180 NC16A ELISA, BP230 ELISA, and full-length BP180 ELISA were positive in 1.8, 2.2, and 10.9% of DPP-4i (+) T2DM cases, respectively; in contrast, they were positive in 0, 7.4, and 5.6% of DPP-4i (-) T2DM cases, respectively. The odds ratio for the development of BP-IgG autoantibodies detected by full-length BP180 ELISA was 2.070 for DPP-4i (+). There were no significant differences between the genders, intake periods of DPP-4i, nor of hemoglobin A1c levels, the anti-full-length BP180 IgG-positive cases tended to be significantly older than anti-full-length BP180 IgG-negative cases (median 74 vs. 69, p = 0.025) in the DPP-4i (+) T2DM cases. Limitations: We focused the analysis on DPP-4i intake and not on the effects of metformin and other drugs. Conclusion: Exposure to specific DPP-4i may induce the development of anti-full-length BP180 autoantibodies even in T2DM patients without any clinical symptoms of BP. Aging would be a risk factor to develop anti-full-length BP180-IgG autoantibody in DPP-4i (+) T2DM cases.

Keywords: ELISA; autoantibody; bullous pemphigoid; diabetes mellitus; dipeptidyl peptidase-IV inhibitor.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Aged
  • Autoantibodies* / blood
  • Autoantibodies* / immunology
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / immunology
  • Dipeptidyl Peptidase 4 / immunology
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Female
  • Humans
  • Male
  • Pemphigoid, Bullous* / blood
  • Pemphigoid, Bullous* / drug therapy
  • Pemphigoid, Bullous* / epidemiology
  • Pemphigoid, Bullous* / immunology
  • Prevalence


  • Autoantibodies
  • Dipeptidyl-Peptidase IV Inhibitors
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4