I saw a Medscape report on Eosinophilic Esophagitis and it posed a genetic mutation as the cause here. It's probably the same issue with the eosinophilia which happens in the instestines as well.
Pathogenetic Mechanisms: More Pieces to the Puzzle
The most significant recent finding is the recent association of EoE with a common variant at 5q22 locus that encompasses TSLP.[31••,32] TSLP is overexpressed in the mucosal biopsies of patients with EoE and may offer an etiological clue to the underlying pathogenesis in some patients. TSLP is an epithelial derived IL-7-like cytokine which can activate a number of immune cells, in particular dendritic and mast cells, and is related to allergic disease such as asthma.
A number of studies have begun to describe the immunological milieu of the esophageal mucosa affected by EoE. Although eosinophils are the most prominent leukocyte associated with EoE, recent studies expanded our narrow view of the esophageal mucosal surface.
Mast cells continue to be associated with inflammation in EoE. Dellon et al. [33] measured tryptase staining in 54 adults with EoE and compared them to 55 with GERD. They determined that the tryptase-positive mast cells were significantly increased in the epithelia of EoE patients compared to GERD. Abonia et al. [34] found similar results in children with EoE and reported
increases in mast cell carboxypeptidase and tryptase but not chymase, findings that normalized after topical fluticasone treatment. Along these lines, Yen et al. [35]
found significantly greater FceRI expression on epithelial cells in EoE children compared to those with GERD and normal controls suggesting a role in IgE-mediated activation. In a series of articles from Nadeau et al., the role of other T cells in the squamous mucosa and peripheral mononuclear cells in EoE has been examined.[36–38] Real-time analysis of peripheral mononuclear cells from 35 children with EoE was compared to eight with GERD, 10 with IBD, and eight healthy controls. EoE patients had significantly more ERK, Bcl-2, bFGF, and eotaxin compared to controls.[37] Further studies identified increased numbers of Tregs (FoxP3 expression) and HLA-DR expression in the affected EoE mucosa.[36,38] Together, these studies continue to define the microenvironment associated with EoE.
More mechanistic studies performed in murine models and ex-vivo human models are identifying key roles for epithelial derived such as IL-13 and IL-15 in initiating and perpetuating esophageal inflammation.[39–41] For instance, tissues from EoE patients were shown to demonstrate increased expression of IL-15 and IL-15r a finding that correlated with mucosal eosinophilia.[39] In a murine model of EoE, IL-15r null mice were protected from eosinophilia. Ex-vivo analysis of murine and human esophageal cells identified an increase in eotaxin-3 following IL-15 stimulation. Together, these findings support a role for IL-15 in the generation of this mucosal inflammation.
Finally, Aceves et al. [42] brought new light to not only the esophageal milieu but also more importantly to functional elements that may contribute to EoE's clinical features. They continued along the lines of their previous work that supports a role for TGF-beta in remodeling events in EoE. Results from an ex-vivo human model system
support a role for mast cells and TGF-beta in esophageal smooth muscle contraction.http://www.medscape.com/viewarticle/744685_7
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