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To explore the mechanism behind gliptin-associated BP we investigated circulating autoantibodies against the major BP autoantigen BP180 in serum samples from patients with type 2 diabetes (T2D) with preceding gliptin medication (n = 136) or without (n = 136). Sitagliptin was the most frequently prescribed gliptin (125\/136 patients). Using an ELISA assay, we showed that IgG autoantibodies against the immunodominant NC16A domain of BP180 were found in 5.9% of gliptin treated and in 6.6% of non-gliptin treated T2D patients. We found that 28% of gliptin treated patients had IgG autoantibodies recognizing the native full-length BP180 in ELISA, but among non-gliptin treated the seropositivity was even higher, at 32%. Further ELISA analysis of additional serum samples (n = 57) found no major changes in the seropositivity against BP180 during a follow-up period of about nine years. In immunoblotting, full-length BP180 was recognized by 71% of gliptin treated and 89% of non-gliptin treated T2D patients, but only by 46% of the age-and sex-matched controls. The chemokine stromal derived factor-1(SDF-1\/CXCL12) is one of the major substrates of DPP4. Immunostainings showed that the expression of SDF-1 was markedly increased in the skin of BP patients, but not affected by prior gliptin treatment. We found that the use of gliptins decreased the serum level of SDF-1\u03b1 in both BP and T2D patients. Our results indicate that the autoantibodies against the linear full-length BP180 are common in patients with T2D, but seropositivity is unaffected by the use of sitagliptin.<\/jats:p>","DOI":"10.3389\/fimmu.2022.942131","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T06:41:21Z","timestamp":1658731281000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Use of gliptins reduces levels of SDF-1\/CXCL12 in bullous pemphigoid and type 2 diabetes, but does not increase autoantibodies against BP180 in diabetic 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