[6] At these sites, IEL are exposed and regulate immune responses to non-dietary and dietary antigens, pathogenic and non-pathogenic organisms and injured self tissues.

[7] Gastrointestinal tract IEL appear in the epithelium of the small intestine, colon, stomach and esophagus, residing between the epithelial cells that line these organs' lumens.

[4] With coeliac disease, the IEL react to the glutelins in dietary gluten by increasing their numbers, becoming pathologically active, producing chronic inflammation that injures intestinal cells, interfering with nutrient absorption and creating an environment conducive to their malignant transformation into EATL.

[1] Optimal treatment of EATL has used regimens consisting of intensive chemotherapy, hematopoietic stem cell transplantation and, in cases with bulky, obstructive and/or perforated bowel disease, surgical intervention.

Individuals are genetically predisposed to develop celiac disease because of the specific types of HLA-DQ proteins expressed by their antigen-presenting cells (APC).

The HLA-DQ proteins that predispose individuals to coeliac disease bind and respond specifically to gluten-related antigens presented to them by APC.

[11] In the GI tract, IEL localize between the epithelial cells lining the colon, small intestine, stomach, and esophagus where they serve to maintain the mucosal barrier, combat infection by pathogens, and regulate immune responses to antigens originating from the diet, pathogens, and damaged tissues.

[3] Laboratory studies indicate that these 3 cytokines acting individually or in synergy are potent stimulators of the JAK1/STAT3 signaling pathway in iCD3+IEL and thereby promote these cells survival (by blocking apoptosis) and proliferation.

[18][19] The small intestinal lesions also contain a tumor necrosis factor which stimulates iCD3+IEL survival and proliferation but does so by activating NF-κB, MAPK, and/or c-Jun N-terminal kinases rather than JAK1/STAT3 signaling pathway.

[8] In most cases these IEL also show genetic abnormalities, particularly activating mutations in JAK1 and/or STAT3 and to lesser extents those cited in the above section on EATL.

[3][10][16] Patients with refractory coeliac disease, especially those with Type II RCD, should be examined at regular intervals for the development of EATL using magnetic resonance imaging, capsule endoscopy, CT scan, and Positron emission tomography;.

[4][32] Previous chemotherapy treatment regimens that did not use autologous stem cell transplantation reported poor prognoses with overall survival, progression free, and mortality rates over a 5-year period of 22%, 3%, and 81%.

[4] A phase 2 study sponsored by the Imagine Institute[33] and being conducted in Paris, France is recruiting patients to examine the efficacy and side effects of a new treatment regimen on EATL.

The regimen consists of treatment with brentuximab vedotin plus CHP (i.e. cyclophosphamide, Adriamycin, prednisone) followed by consolidation chemotherapy and autologous hematopoietic stem cell transplantation.

[34] A phase 1 study sponsored by the National Institutes of Health Clinical Center is recruiting patients that have CD30-expressing lymphomas such as EATL to examine the effects of a conditioning drug regimen (i.e. cyclophosphamide and fludarabine) followed by infusions of the patients' chimeric antigen receptor T cells that have been modified to target and destroy cells bearing CD30.

[36] A recently completed Phase 2, randomized, double-blinded, placebo-controlled, parallel group study evaluated the efficacy and safety of a monoclonal antibody (termed AMG 714) directed against IL-15 in adult patients with Type II RCD.

[17] Expanded access or compassionate use requests for AMG 714 may be considered for adult patients with biopsy-proven Type II RCD who have failed all available treatment options and do not have EATL.

To request access, use Responsible Party contact information found by hitting the "More info..." linkage on the following clinical trials page.