Small bowel, celiac disease and adaptive immunity.
BACKGROUND
Celiac disease is a multifactorial and polygenic disease with autoimmune features. The disease is caused by an inappropriate immune response to gluten. Elimination of gluten from the diet leads to disease remission, which is the basis for today's treatment of the disease. There is an unmet need for new alternative treatments.


CONCLUSIONS
Genetic findings point to adaptive immunity playing a key role in the pathogenesis of celiac disease. MHC is by far the single most important genetic factor in the disease. In addition, a number of non-MHC genes, the majority of which have functions related to T cells and B cells, also contribute to the genetic predisposition, but each of them has modest effect. The primary MHC association is with HLA-DQ2 and HLA-DQ8. These HLA molecules present gluten epitopes to CD4+ T cells which can be considered to be the master regulators of the immune reactions that lead to the disease. The epitopes which the T cells recognize are usually deamidated, and this deamidation is mediated by the enzyme transglutaminase 2 (TG2). Celiac disease patients have disease-specific antibodies. In addition to antibodies to gluten, these include autoantibodies to TG2. Antibodies to deamidated gluten are nearly as specific for celiac disease as the anti-TG2 antibodies. Both types of antibodies appear only to be produced in subjects who are HLA-DQ2 or HLA-DQ8 when they are consuming gluten.


CONCLUSIONS
It is hardly coincidental that TG2 is implicated in T-cell epitope formation and at the same time a target for autoantibodies. Understanding this connection is one of the major challenges for obtaining a complete understanding of how gluten causes tissue destruction and remodeling of the mucosa in the small bowel.
Ludvig M
LM
Sollid
Rasmus
R
Iversen
Øyvind
Ø
Steinsbø
Shuo-Wang
SW
Qiao
Elin
E
Bergseng
Siri
S
Dørum
M Fleur
MF
du Pré
Jorunn
J
Stamnaes
Asbjørn
A
Christophersen
Inês
I
Cardoso
Kathrin
K
Hnida
Xi
X
Chen
Omri
O
Snir
Knut E A
KEA
Lundin
D056704:Adaptive Immunity; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019204:GTP-Binding Proteins / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins