Autoimmune Pancreatitis: An Autoimmune or Immunoinflammatory Disease?

Abstract

Autoimmune pancreatitis (AIP) has been widely presumed to be an autoimmune disease that is characterized by elevated IgG and/or IgG4, the presence of autoantibodies, and an infiltration of lymphocytes and plasma cells with fi- brosis. However, no detailed immunological studies have been published. To define immunological changes in AIP in de- tail, and to review evidence for autoimmunity which may be antigen specific and may play a role in the pathogenesis of AIP, and therefore, to determine whether AIP is an autoimmune disease. A detailed immunological investigation for both innate and adaptive immune responses was performed in a patient with AIP. Review of literature was performed from Pub med, and Medline search. Immunological analysis of patient with AIP revealed increased production of proinflammatory IL-6, and IL-17, and increased NK cell activity. No organ-specific or non-specific antibodies were detected. There was no correlation between serum IgG4 with disease activity or response to steroid therapy. Review of literature revealed lack of auto-antigen-specific T and B cell responses in AIP, and autoantibodies are present only in a subset of patients, and are not specific to pancreatic tissue antigens. Therefore, we propose the term Immunoinflammatory pancreatitis rather than an autoimmune pancreatitis. Autoimmune pancreatitis is typically characterized by a diffuse or segmental narrowing of the main pancreatic duct on imaging, elevated IgG and/or IgG4, the presence of autoantibodies, an infiltration of lymphocytes and plasma cells, and presence of fibrosis. The autoantibodies that have been examined include ANA, anti-microsomal antibodies, anti-thyroglobulin antibodies, and antibodies against pancre- atic secretory trypsin inhibitor, lactoferrin, and carbonic an- hydrase (2-5). However, the presence of these autoantibodies has been only sporadically documented in limited numbers of cases. In addition, many of these autoantibodies are di- rected against antigens that are also present in the salivary gland, biliary duct, and distal renal tubules. The detection of IgG, IgG4, antinuclear antibodies, and rheumatoid factor