Autoimmune pancreatitis Esmee Burgers Louise Dugué Supervized by Dr. habil. Rakonczay Zoltan

Outline Introduction Types of AIP Pathogenesis Genetic predispositions Inflammatory mechanisms Treatment Take home messages

introduction Rare version of chronic pancreatitis Clinically Incidence: 1 in ~122000 people (Japan) Clinically Mild or no abdominal pain Jaundice Cachexia Differential diagnosis Pancreatic cancer

Two types of aip Type 1 Type 2 Nomenclature IgG4 related   Type 1 Type 2 Nomenclature IgG4 related AIP with GELs, IgG4 unrelated Prevalence Asia > US > Europe Europe > US > Asia Age Older than 60 Older than 40 Sex Male > female No sex bias Abdominal Pain Very rare Rare Steroid therapy Responsive Relapse High rate Extra-pancreatic lesions IgG4-related disease Inflammatory bowel disease Complications Frequent Uncommon

Histology Obliterative phlebitis Storiform fibrosis Hart P et al. Gastroenterology 2015;149:39-51

Histology Immunohistochemistry for IgG4 Zhang L et al. Modern pathology 2007;20:23-28

Histology GEL Zhang L et al. Modern pathology 2007;20:23-28

Pathogenic mechanisms1 Carbonic anhydrase!! Modified from Okazaki K, Uchida K. Autoimmune pancreatitis, the past, present and future. Pancreas 2015; 44:1006-1016

Genetic predispositions HLA DQβ1 and DRβ1 : MHC II genes DQβ1*0401 and DRβ1*0405 : predicting factors DQβ1 57 mutation  relapses PRSS1 Cationic trypsinogen enzyme  acute pancreatitis Low rate of relapses

Genetic predispositions MST1 Serine/threonine kinase Traffic of immune cells Extra-pancreatic lesions CTLA-4 Maintenance of tolerance Expressed on CD4+ and CD8+ T cells Those cells infiltrate pancreatic tissue Rat study  CD4+ T cells can induce pancreatitis Negative regulator of T-cells

Inflammatory mechanisms Hart P, Zen Y and Chari S. Recent advances in autoimmune pancreatitis. Gastroenterology 2015;149:39-51

treatment TYPE 1 AIP TYPE 2 AIP Response to steroids Positive Other treatments possible Immunomodulators Rituximab Relapse Common Rare

Take home messages AIP is curable – responsive to corticosteroids 2 types Type 1  IgG4 Type 2  GELs Differentiation based on histology Inflammatory process Innate immune system IgG-4 Th and Tregs

Thank you for your attention! Any questions?