1. Persisting enteropathy and disturbed adaptive mucosal immunity due to MHC class II deficiency
- Author
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Eva Jacobsen, Peter Möller, Carsten Posovszky, Catharina Schuetz, Mehtap Sirin, Thomas F. E. Barth, Myriam Ricarda Lorenz, Klaus-Michael Debatin, Anjona Schmidt-Choudhury, Klaus Schwarz, Manfred Hönig, Tobias Rothoeft, and Ansgar Schulz
- Subjects
0301 basic medicine ,Male ,Adolescent ,Gastrointestinal Diseases ,Immunology ,DNA Mutational Analysis ,chemical and pharmacologic phenomena ,Inflammation ,Adaptive Immunity ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,medicine ,HLA-DR ,Immunology and Allergy ,Humans ,Enteropathy ,Intestinal Mucosa ,Child ,MHC class II ,biology ,business.industry ,Immunologic Deficiency Syndromes ,Infant ,HLA-DR Antigens ,medicine.disease ,Acquired immune system ,Pedigree ,DNA-Binding Proteins ,030104 developmental biology ,Child, Preschool ,Mutation ,biology.protein ,Female ,Antibody ,medicine.symptom ,business ,030215 immunology ,Transcription Factors - Abstract
Intestinal epithelial cells (IECs) form a fundamental mucosal barrier and actively participate in tolerance and immunity against intestinal contents. Major histocompatibility complex class II (MHC II) and invariant chain (Ii) molecules are essential for adaptive immune response. MHC II deficiency often presents with gastrointestinal disorders. Intestinal biopsy samples revealed an absence of HLA-DR, Ii, and local immunoglobulins in both hematopoietic immune cells and IECs accompanied by a lack of faecal sIgA. After successful hematopoietic stem cell transplantation (HSCT) absent HLA-DR and Ii expression persisted in IECs and faecal stool analysis indicated inflammation and high microbial activity. We describe multifaceted disturbance of adaptive mucosal immunity in MHC II deficient patients suffering from enteropathy. HLA-DR and Ii expression on enterocytes is not restored by HSCT. This may account for increased susceptibility to enteric infections and intestinal inflammation leading to prolonged enteropathy reported in MHC II deficient patients.
- Published
- 2018