Autoimmunization against collagen XVII in patients with high risk for bullous pemphigoid and the effect of vildagliptin on the mouse skin proteome
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
Auditorium 9 of Oulu University Hospital (Kajaanintie 50)
Topic of the dissertation
Autoimmunization against collagen XVII in patients with high risk for bullous pemphigoid and the effect of vildagliptin on the mouse skin proteome
Doctoral candidate
Master of Philosophy Antti Nätynki
Faculty and unit
University of Oulu Graduate School, Faculty of Medicine, Medical Research center Oulu; Research Unit of Clinical Medicine
Subject of study
Medicine
Opponent
Professor Juha Peltonen, University of Turku
Custos
Professor Kaisa Tasanen-Määttä, University of Oulu, Oulu university hospital
Autoimmunization against collagen XVII in patients with high risk for bullous pemphigoid and the effect of vildagliptin on the mouse skin proteome
Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by intense itching and tense bullae located typically on the trunk and extremities. BP affects mainly patients over 70 years of age and has up to 40% two-year mortality. BP incidence has increased during the 21st century.
Antibodies against collagen XVII (also known as BP180), a protein essential for connecting epidermal layer of the skin to the basal membrane, are demonstrated to be central in the pathogenesis of BP.
Dermatitis herpetiformis (DH), an autoimmune dermatosis of patients with celiac disease (CD), and the use of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors or gliptins), drugs to treat type 2 diabetes (T2D), markedly increase the risk of BP. However, it is currently not clear how these factors promote the development of BP.
The study aimed to clarify the mechanism of the associations between DH, the use of gliptins, and BP. The prevalence of anti-BP180 antibodies in serum and target region of anti-BP180 antibodies were analyzed in patients with CD, DH, BP or T2D by various molecular biology methods. Transglutaminase antibodies characteristic for DH were also analyzed from CD, DH, and BP sera. The levels of stromal cell-derived factor 1 (SDF-1), a main DPP-4 substrate, were also studied from patient sera and skin. Furthermore, the effect of gliptin treatment on the protein levels of the mouse skin were studied.
The study showed a low prevalence of anti-BP180 antibodies in patients with CD, DH, or T2D. Antibodies from DH and T2D patients using gliptins reacted to parts of BP180 atypical in BP. Even a decade of use of sitagliptin, the most common gliptin prescribed in Finland, did not increase the prevalence of anti-BP180 antibodies in patients with T2D with average age of ~67 years. An additional triggering factor to anti-BP180 antibodies seems to be needed for BP development.
SDF-1 was shown to be increased in the BP skin and in the serum of T2D, BP and aged controls. The use of gliptins decreased its levels.
The study showed that exposing mice to vildagliptin caused change in 165 cutaneous proteins without visible skin symptoms. Many of these changed proteins were linked to the organization of the cytoskeleton. Further study of these candidate proteins could shed light on the pathogenesis of BP.
Antibodies against collagen XVII (also known as BP180), a protein essential for connecting epidermal layer of the skin to the basal membrane, are demonstrated to be central in the pathogenesis of BP.
Dermatitis herpetiformis (DH), an autoimmune dermatosis of patients with celiac disease (CD), and the use of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors or gliptins), drugs to treat type 2 diabetes (T2D), markedly increase the risk of BP. However, it is currently not clear how these factors promote the development of BP.
The study aimed to clarify the mechanism of the associations between DH, the use of gliptins, and BP. The prevalence of anti-BP180 antibodies in serum and target region of anti-BP180 antibodies were analyzed in patients with CD, DH, BP or T2D by various molecular biology methods. Transglutaminase antibodies characteristic for DH were also analyzed from CD, DH, and BP sera. The levels of stromal cell-derived factor 1 (SDF-1), a main DPP-4 substrate, were also studied from patient sera and skin. Furthermore, the effect of gliptin treatment on the protein levels of the mouse skin were studied.
The study showed a low prevalence of anti-BP180 antibodies in patients with CD, DH, or T2D. Antibodies from DH and T2D patients using gliptins reacted to parts of BP180 atypical in BP. Even a decade of use of sitagliptin, the most common gliptin prescribed in Finland, did not increase the prevalence of anti-BP180 antibodies in patients with T2D with average age of ~67 years. An additional triggering factor to anti-BP180 antibodies seems to be needed for BP development.
SDF-1 was shown to be increased in the BP skin and in the serum of T2D, BP and aged controls. The use of gliptins decreased its levels.
The study showed that exposing mice to vildagliptin caused change in 165 cutaneous proteins without visible skin symptoms. Many of these changed proteins were linked to the organization of the cytoskeleton. Further study of these candidate proteins could shed light on the pathogenesis of BP.
Last updated: 18.3.2024