Parallels between Pathogens and Gluten Peptides in Celiac Sprue

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights

Extranasal extranodal NK/T cell lymphoma: A post-transplantation lymphoproliferative disease

WOS: 000476667700011PubMed ID: 30983103Extranodal NK/T cell lymphoma (ENKTL) is a rare form of non-Hodgkin lymphoma. It mostly occurs in the upper respiratory tract. Cutaneous involvement can be seen among the extranasal ENKTLs. After solid organ and haematopoietic stem cell transplantation, post-transplantation lymphoproliferative disease because of immunosuppressive therapy is usually B cell-derived; T and NK/T cell-derived disease is rarely seen. A 43-year-old female patient who had renal transplantation 14 years ago presented with cutaneous ulceration and subcutaneous nodules located in the abdomen. The patient was diagnosed with ENKTL, nasal type. Although it is rare, ENKTL nasal type is a lymphoproliferative disease that should be considered in the differential diagnosis of ulcerated cutaneous tumoural lesions