Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease

Bhattacharya, Baidurya; Carlsten, James; Sabo, Edmond; Kethu, Sripathi R.; Meitner, Patricia A.; Tavares, Rosemarie; Jakate, Shriram; Mangray, Shamlal; Aswad, Bassam I.; Resnick, Murray B.

doi:10.1016/j.humpath.2007.05.008

Cited by 118 publications

(88 citation statements)

References 30 publications

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“…Eotaxin has been implicated previously in the pathogenesis of eosinophilic esophagitis. 19,27 Fibrosis with subepithelial collagen deposition is also a feature of eosinophilic esophagitis. 28 The prominent lamina propria eosinophilia in many of our patients' biopsies was further rationale for testing the tissue for eotaxin.…”

Section: Discussionmentioning

confidence: 99%

“…However, some eosinophilic esophagitis studies have applied a more sensitive quantitative real-time PCR protocol for detection of increased tissue eotaxin levels. 19 This type of study would be required before a role for eotaxin can be completely excluded.…”

Section: Discussionmentioning

confidence: 99%

“…Eosinophilic esophagitis has been linked to allergy and the chemokine eotaxin has been implicated in the pathogenesis. 19 While it remains unclear whether IgG4 itself is pathogenic or a side effect in IgG4-related disease, increased levels of this class of immunoglobulin in serum and tissue plasma cells are a defining feature in IgG4-related disease. 20 Through detailed evaluation of biopsies from 40 patients, the present study aims to characterize distinct inflammatory patterns in collagenous gastritis and determine whether any of these variants are associated with particular clinical subgroups defined by factors such as age at presentation, disease association, or long-term outcome.…”

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confidence: 99%

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Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients

et al. 2015

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Collagenous gastritis is a rare condition defined histologically by a superficial subepithelial collagen layer. This study further characterizes the morphologic spectrum of collagenous gastritis by evaluating a multiinstitutional series of 40 patients (26 female and 14 male). The median age at onset was 16 years (range 3-89 years), including 24 patients (60%) under age 18. Twelve patients (30%) had associated celiac disease, collagenous sprue, or collagenous colitis. Hematoxylin and eosin slides were reviewed in biopsies from all patients and tenascin, gastrin, eotaxin, and IgG4/IgG immunohistochemical stains were applied to a subset. The distribution of subepithelial collagen favored the body/fundus in pediatric patients and the antrum in adults. There were increased surface intraepithelial lymphocytes (425 lymphocytes/100 epithelial cells) in five patients. Three of these patients had associated celiac and/or collagenous sprue/colitis, while the remaining two had increased duodenal lymphocytosis without specific etiology. An eosinophil-rich pattern (430 eosinophils/high power field) was seen in 21/40 (52%) patients. Seven patients' biopsies demonstrated atrophy of the gastric corpus mucosa. Tenascin immunohistochemistry highlighted the subepithelial collagen in all 21 specimens evaluated and was a more sensitive method of collagen detection in biopsies from two patients with subtle subepithelial collagen. No increased eotaxin expression was identified in 16 specimens evaluated. One of the twenty-three biopsies tested had increased IgG4-positive cells (100/high power field) with an IgG4/IgG ratio of 55%. In summary, collagenous gastritis presents three distinct histologic patterns including a lymphocytic gastritis-like pattern, an eosinophil-rich pattern, and an atrophic pattern. Eotaxin and IgG4 were not elevated enough to implicate these pathways in the pathogenesis. Tenascin immunohistochemistry can be used as a sensitive method of collagen detection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients

et al. 2015

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“…[7][8][9] These studies show an important role of mediators of a Th2 inflammatory response, including IL-4, IL-5, IL-13 and eotaxins. 7,8,[10][11][12] Further studies have investigated gene expression alterations directly associated with IL-13 stimulation of esophageal epithelial cell cultures. These have shown upregulation of inflammation-related genes including tumor necrosis factor alpha-induced factor 6 (TNFAIP6) and downregulation of the innate immunity associated cysteine-rich secretory protein 3 (CRISP3) and epidermal differentiation factors including filaggrin (FLG).…”

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confidence: 99%

Expression microarray analysis identifies novel epithelial-derived protein markers in eosinophilic esophagitis

Matoso

Mukkada

et al. 2013

Modern Pathology

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Gene expression studies in eosinophilic esophagitis support an immune-mediated etiology associated with differential regulation of inflammatory and epithelial-derived genes. We aimed to further characterize epithelial gene expression alterations in eosinophilic esophagitis and to explore the use of immunohistochemistry to identify these alterations. Esophageal biopsies from pediatric patients with eosinophilic esophagitis before and after therapy with topical steroids (N ¼ 7) were screened by gene expression microarray and results were validated by RT-PCR. A larger group of eosinophilic esophagitis patients (N ¼ 42) was then used to evaluate protein expression by immunohistochemistry compared with reflux patients (N ¼ 15) and normal controls (N ¼ 17). Microarray and RT-PCR studies identified overexpression of ALOX15 and tumor necrosis factor alphainduced factor 6 (TNFAIP6) and underexpression of filaggrin (FLG), SLURP1 and cysteine-rich secretory protein 3 (CRISP3) in eosinophilic esophagitis. Immunohistochemistry for ALOX15 was positive in 95% of eosinophilic esophagitis and negative in all controls, all eosinophilic esophagitis after therapy and all reflux biopsies (Po0.001). TNFAIP6 was positive in 88% of eosinophilic esophagitis samples versus 47% of controls, 29% of eosinophilic esophagitis after therapy and 40% of reflux samples (P ¼ 0.002). Overexpression of both ALOX15 and TNFAIP6 directly correlated with the degree of eosinophilic infiltration. FLG was positive in 88% of controls and 100% of reflux biopsies, but negative in all eosinophilic esophagitis samples, and its expression was regained in 86% of eosinophilic esophagitis after therapy patients (Po0.001). SLURP1 expression was positive in all controls and reflux samples, but only positive in 5% of eosinophilic esophagitis and was re-expressed to 100% positivity in eosinophilic esophagitis after therapy patients (Po0.001). The majority of controls (89%) and reflux biopsies (100%) were positive for CRISP3 while eosinophilic esophagitis before therapy were positive in 14% of samples (Po0.001) with partial recovery after treatment (43%, P ¼ 0.105). This study identified five epithelial-derived markers differentially expressed in eosinophilic esophagitis easily detectable by immunohistochemistry with potential diagnostic utility.

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“…Similarly, a recent report has proven a high sensitivity (91%) and specificity (100%) for diagnosing EoE before endoscopy using a simplified equation: peripheral eosinophilia + history of food impaction + PPI refractory heartburn [36]. As for histological features, eosinophilic microabscesses [37], tryptase mast cell staining [38] and levels of eotaxin-3 in esophageal biopsies [39] have been suggested to favour EoE, albeit further studies are needed to set a delimited distinction between EoE and GERD.…”

Section: The Controversial Relationship Between Gerd and Eoementioning

confidence: 99%

Proton Pump Inhibitors Therapy for Eosinophilic Esophagitis

Molina–Infante¹,

Zamorano²,

Rivas³

et al. 2013

J Allergy Ther

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Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease

Cited by 118 publications

References 30 publications

Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients

Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients

Expression microarray analysis identifies novel epithelial-derived protein markers in eosinophilic esophagitis

Proton Pump Inhibitors Therapy for Eosinophilic Esophagitis

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