Serum and Tissue CD23, IL‐15, and FasL in Cow's‐Milk Protein–sensitive Enteropathy and in Coeliac Disease

Kokkonen, Tuomo S.; Augustin, Merja T.; Kokkonen, Jorma; Karttunen, Riitta; Karttunen, Tuomo J.

doi:10.1097/mpg.0b013e318237c145

Cited by 14 publications

(9 citation statements)

References 40 publications

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“…Strikingly, CD95L-expressing HEVs observed in cow’s-milk-sensitive enteropathy (CMSE) and celiac disease were surrounded by lymphoid follicles. Moreover, overexpression of m-CD95L in CMSE correlated with increased concentrations of serum CD95L, enlargement of mucosal lymphoid nodules in the gastrointestinal tract (GIT), and infiltration by intraepithelial lymphocytes ( 56 ). These data suggest that, after cleavage by metalloproteases, s-CD95L attracts leukocytes to the inflamed GIT.…”

Section: Drs Belonging To the Tumor Necrosis Factor (Tnf) Receptor (Tmentioning

confidence: 99%

CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases

et al. 2017

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Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance. Because mutations of this receptor or its ligand lead to autoimmune disorders such as systemic lupus erythematosus (SLE) and cancers, CD95 and CD95L were initially thought to play a role in immune homeostasis and tumor elimination via apoptotic signaling pathways. However, recent data reveal that CD95 also evokes non-apoptotic signals, promotes inflammation, and contributes to carcinogenesis; therefore, it is difficult to dissect its apoptotic effects from its non-apoptotic effects during pathogenesis of disease. CD95L is cleaved by metalloproteases and so exists in two different forms: a transmembrane form and a soluble ligand (s-CD95L). We recently observed that the soluble ligand is overexpressed in serum from patients with triple-negative breast cancer or SLE, in whom it contributes to disease severity by activating non-apoptotic signaling pathways and promoting either metastatic dissemination or accumulation of certain T cell subsets in damaged organs. Here, we discuss the roles of CD95 in modulating immune functions via induction of mainly non-apoptotic signaling pathways.

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Section: Drs Belonging To the Tumor Necrosis Factor (Tnf) Receptor (Tmentioning

confidence: 99%

CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases

et al. 2017

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“…Patients with untreated food allergy express equal densities of total intraepithelial CD3+ and alpha/beta + T-cells but significantly higher densities of gamma/delta + cells and gamma/delta + /CD3+ ratio than patients currently on an elimination diet for food allergy or healthy controls [88][89][90].…”

Section: Non-celiac Gluten Sensitivitymentioning

confidence: 99%

Non-Celiac Gluten Sensitivity: Literature Review

Mansueto

Seidita

D’Alcamo

et al. 2014

Journal of the American College of Nutrition

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Key words: non-celiac gluten sensitivity, celiac disease, wheat allergy, food allergy, HLA, flow cytometric basophil activation test, innate immune response Background: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS).Aim: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients.Methods: We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS.Results: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients.Conclusions: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points:• Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet.• NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy.• Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course.• A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients.• Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup. Abbreviations: CD = celiac disease, WA = wheat allergy, NCGS = non-celiac gluten sensitivity, GFD = gluten-free diet, IBS = irritable bowel syndrome, HLA = human leukocyte antigen, tTg = antitissue transglutaminase, AGA = antigliadin antibodies, EMA = endomysial antigen, DGP = deami...

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“…The connection between intraepithelial γ/δ+ T‐cells and other members of innate immunity are highlighted by the results of Kokkonen et al ., who recently demonstrated in coeliac disease and in cow's milk‐sensitive enteropathy that serum CD23, a protein expressed in the lymphoid follicles, tends to increase. In coeliac disease, serum CD23 levels may provide information about the severity of villous atrophy, whereas in cow's milk‐sensitive enteropathy high serum FasL, functionally connected with IL‐15 proliferation and apoptosis of the intraepithelial lymphocytes, indicates an increase in intraepithelial lymphocytes and the presence of LNH, suggesting the importance of FasL‐mediated mechanisms in the pathogenesis of these cow's milk‐sensitive enteropathy features …”

Section: Lnh and Density Of γ/δ+ T‐cellsmentioning

confidence: 99%

Review article: intestinal lymphoid nodular hyperplasia in children – the relationship to food hypersensitivity

Mansueto

Iacono

Seidita

et al. 2012

Aliment Pharmacol Ther

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Summary Background Lymphoid aggregates are normally found throughout the small and large intestine. Known as lymphoid nodular hyperplasia (LNH), these aggregates are observed especially in young children and are not associated with clinical symptoms being considered ‘physiological’. In children presenting with gastrointestinal symptoms the number and size of the lymphoid follicles are increased. Patients suffering from gastrointestinal symptoms (i.e. recurrent abdominal pain) should systematically undergo gastroduodenoscopy and colonoscopy. With these indications LNH, especially of the upper but also of the lower gastrointestinal tract has been diagnosed, and in some children it may reflect a food hypersensitivity (FH) condition. Aim To review the literature about the relationship between LNH and FH, particularly focusing on the diagnostic work‐up for LNH related to FH. Methods We reviewed literature using Pubmed and Medline, with the search terms ‘lymphoid nodular hyperplasia’, ‘food hypersensitivity’, ‘food allergy’ and ‘food intolerance’. We overall examined 10 studies in detail, selecting articles about the prevalence of LNH in FH patients and of FH in LNH patients. Results Collected data showed a median of 49% (range 32–67%) LNH in FH patients and a median of 66% (range 42–90%) FH in LNH patients. Literature review pointed out that the most important symptom connected with LNH and/or FH was recurrent abdominal pain, followed by diarrhoea and growth retardation. Both LNH and FH are associated with an increase in lamina propria γ/δ+ T cells, but the mechanisms by which enhanced local immune responses causing gastrointestinal symptoms still remain obscure. Conclusions When assessing FH, we rely on clinical evaluation, including elimination diet and challenge tests, and endoscopic and immunohistochemical findings. Considering the possible co‐existence of duodenal and ileo‐colonic LNH, upper endoscopy can be recommended in children with suspected FH, especially in those presenting with additional upper abdominal symptoms (i.e. vomiting). Likewise, lower endoscopy might be additionally performed in patients with suspected FH and LNH of the duodenal bulb, also presenting with lower abdominal symptoms (i.e. recurrent abdominal pain).

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Serum and Tissue CD23, IL‐15, and FasL in Cow's‐Milk Protein–sensitive Enteropathy and in Coeliac Disease

Cited by 14 publications

References 40 publications

CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases

CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases

Non-Celiac Gluten Sensitivity: Literature Review

Review article: intestinal lymphoid nodular hyperplasia in children – the relationship to food hypersensitivity

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