scholarly journals T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten Sensitivity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Giuseppe Losurdo ◽  
Domenico Piscitelli ◽  
Federica Pezzuto ◽  
Francesco Fortarezza ◽  
Claudia Covelli ◽  
...  

Background and Aims. Nonceliac gluten sensitivity (NCGS) is a gluten-related emerging condition. Since few data about NCGS histopathology is available, we assessed the markers of lymphocyte and innate immunity activation. Materials and Methods. We retrieved duodenal biopsy samples of patients with NCGS diagnosis according to the Salerno criteria. We selected specimens of positive (seropositive celiac disease/Marsh 1-2 stage) and negative (normal microscopic picture) controls. Immunohistochemistry for CD3 (intraepithelial lymphocytes-IELs), CD4 (T helper lymphocytes), CD8 (T cytotoxic lymphocytes), and CD1a/CD117 (Langerhans/mast cells) was performed. ANOVA plus Bonferroni’s tests were used for statistical analysis. Results. Twenty NCGS, 16 celiac disease, and 16 negative controls were selected. CD3 in NCGS were higher than negative controls and lower than celiac disease (18.5 ± 6.4, 11.9 ± 2.8, and 40.8 ± 8.1 IELs/100 enterocytes; p<0.001). CD4 were lower in NCGS than controls and celiac disease (31.0 ± 22.1, 72.5 ± 29.5, and 103.7 ± 15.7 cells/mm2; p<0.001). CD8 in NCGS were similar to negative controls, but lower than celiac disease (14.0 ± 7.4 and 34.0 ± 7.1 IELs/100 enterocytes, p<0.001). CD117 were higher in NCGS than celiac disease and negative controls (145.8 ± 49.9, 121.3 ± 13.1, and 113.5 ± 23.4 cells/mm2; p=0.009). Conclusions. The combination of CD4 and CD117, as well as IEL characterization, may be useful to support a clinical diagnosis of NCGS.

Author(s):  
Feridun Gurlek ◽  
Eyyup Tasdemir ◽  
Taskın Erkinuresin

Background: The aim of this study is to evaluate gluten sensitivity and/or celiac disease (CD) on the basis of serological tests and duodenal biopsy and to draw attention to the prevalence in the population and the correlation between serological tests and biopsy results.Methods: Patients who applied to Health Sciences University Bursa High Specialization Training and Research Hospital between 2015-2019 and who underwent serological tests and duodenal biopsies with a diagnosis of CD or gluten sensitivity were retrospectively analyzed.Results: The study was conducted with a total of 1137 cases, 61.2% (n = 696) of who were women and 38.8% (n = 441) were men. Their ages range from 17 to 91, with a mean of 40.16 ± 16.18 years. Of the 178 patients with gluten sensitivity, 122 (68%) were female and 56 (32%) were male. According to the results of duodenal biopsy, an average of 8% Marsh 3, 5% Marsh 1-2 was detected in the last five years. For the whole study, a significant difference was found between celiac autoantibody positivity rates according to the biopsy results (p = 0.001; p <0.01). The rate of serological test positivity was higher in patients with biopsy result Marsh 3 than those with normal biopsy result, peptic duodenitis and Marsh 1 and 2. No statistically significant difference was found between the rates of Marsh 3 biopsy results and serological test positivity by years (p> 0.05).Conclusions: The number of patients applied with a diagnosis of CD in the last five years has gradually increased (3.4-33.7%). Of the patients with Marsh 3 and Marsh 1-2 biopsy results, 78% were under 50 years old. This suggests that gluten enteropathy in young female patients having digestive system complaints should not be ignored during the diagnosis. Serological test results were highly correlated with the biopsy results in patients with Marsh 3 biopsy results. We think that if clinical findings are supported with serological tests and directed for biopsy in the diagnosis of celiac disease, it will be more cost effective and the workload and time loss will be prevented.


2006 ◽  
Vol 52 (6) ◽  
pp. 1175-1180 ◽  
Author(s):  
Antonio Carroccio ◽  
Lidia Di Prima ◽  
Giuseppe Pirrone ◽  
Calogero Scalici ◽  
Ada M Florena ◽  
...  

Abstract Background: We measured anti-transglutaminase (anti-tTG) antibody in the culture medium of intestinal biopsy specimens from patients with suspected celiac disease (CD) and evaluated the relationship between antibody production and severity of intestinal mucosal damage. Methods: We performed diagnostic testing for CD on 273 consecutive patients. In addition to routine histologic evaluation of duodenal biopsy specimens, we assayed anti-tTG antibodies in serum and in the culture medium of duodenal biopsy specimens. Results: CD was diagnosed in 191 of the 273 patients. Sensitivity and specificity of the serum anti-endomysium (EmA) and anti-tTG assays were 83% and 85% and 99% and 95%, respectively, and both had 88% diagnostic accuracy. EmA and anti-tTG assayed in the culture medium had 98% sensitivity, 100% specificity, and 98% diagnostic accuracy (vs serum assays; P &lt;0.0001). Twenty-nine CD patient specimens (16%) were negative for serum anti-tTG and EmA; for 24 of these patients, anti-tTG assay of the culture medium was positive. The CD patients whose biopsy specimens were positive for serum antibodies showed the following intestinal histologies: total villous atrophy, 35%; severe villous atrophy, 25%; mild atrophy, 25%; villi with no atrophy but with increased intraepithelial lymphocytes, 15%. None of the CD patients whose specimens were negative for serum antibodies showed total or severe villous atrophy; 77% had mild villous atrophy, and 23% had no villous atrophy but had increased intraepithelial lymphocyte counts. Mild villous atrophy was also seen in specimens from ∼15% of patients without CD. Conclusion: Anti-tTG assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in patients negative for serum antibodies.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Alexandre Guilhem ◽  
Pierre Portalès ◽  
Sophie Dupuis-Girod ◽  
Sophie Rivière ◽  
Thierry Vincent

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype (muco-cutaneous telangiectases, arteriovenous malformations), a specific risk of infection is suggested by case series of severe and atypical infections as well as by reports of decreased T and natural killer (NK) lymphocyte counts. As some evidence supports a dysregulation of the CXCR4/CXCL12 chemotactic axis of HHT endothelial cells, we hypothesized that a similar phenomenon could occur on lymphocytes. Methods Eighteen HHT patients with history of severe infection (HSI) were matched in age and sex with 18 HHT without HSI and 18 healthy control subjects (HC). We assessed the cell count and the surface expression of CXCR4 and CD26 (CXCL12 inactivating peptidase) of circulating T-helper and T-cytotoxic lymphocytes (including naive, memory and activated subsets) and NK cells. Results The overall HHT group of 36 patients exhibited a reduction of circulating T-helper lymphocytes compared to HC (median: 517 vs. 1026 cells/mm3, p < 0.0001), correlated with age (r =  − 0.46, p = 0.005), requirement of intravenous iron or blood transfusions (median: 291 vs. 627 cells/mm3, p = 0.03) and CXCR4 surface expression (r = 0.353, p = 0.0345). CXCR4 and CD26 membrane expression were both decreased on HHT T-helper lymphocytes (median MFI ratio: 4.49 vs. 5.74 for CXCR4 and 3.21 vs. 4.33 for CD26, p = 0.03 and 0.0018 respectively) with an unchanged CXCR4/CD26 ratio. The HHT group with HSI had a higher CXCR4/CD26 ratio on the total T-lymphocyte population, as well as on the T-helper population and its naive subset (median on naive T-helper cells: 2.34 vs. 1.32, p = 0.0002). Conclusions Our findings support a dysregulation of the CXCL12/CXCR4 chemotaxis of T-helper lymphocytes in HHT patients, potentially linked to their T-helper lymphopenia and susceptibility to infection.


2017 ◽  
Vol 114 (6) ◽  
pp. E980-E989 ◽  
Author(s):  
Yvonne M. C. Kooy-Winkelaar ◽  
Dagmar Bouwer ◽  
George M. C. Janssen ◽  
Allan Thompson ◽  
Martijn H. Brugman ◽  
...  

Refractory celiac disease type II (RCDII) is a severe complication of celiac disease (CD) characterized by the presence of an enlarged clonal population of innate intraepithelial lymphocytes (IELs) lacking classical B-, T-, and natural killer (NK)-cell lineage markers (Lin−IELs) in the duodenum. In ∼50% of patients with RCDII, these Lin−IELs develop into a lymphoma for which no effective treatment is available. Current evidence indicates that the survival and expansion of these malignant Lin−IELs is driven by epithelial cell-derived IL-15. Like CD, RCDII is strongly associated with HLA-DQ2, suggesting the involvement of HLA-DQ2–restricted gluten-specific CD4+ T cells. We now show that gluten-specific CD4+ T cells isolated from CD duodenal biopsy specimens produce cytokines able to trigger proliferation of malignant Lin−IEL lines as powerfully as IL-15. Furthermore, we identify TNF, IL-2, and IL-21 as CD4+ T-cell cytokines that synergistically mediate this effect. Like IL-15, these cytokines were found to increase the phosphorylation of STAT5 and Akt and transcription of antiapoptotic mediator bcl-xL. Several small-molecule inhibitors targeting the JAK/STAT pathway blocked proliferation elicited by IL-2 and IL-15, but only an inhibitor targeting the PI3K/Akt/mTOR pathway blocked proliferation induced by IL-15 as well as the CD4+ T-cell cytokines. Confirming and extending these findings, TNF, IL-2, and IL-21 also synergistically triggered the proliferation of freshly isolated Lin−IELs and CD3−CD56+ IELs (NK-IELs) from RCDII as well as non-RCDII duodenal biopsy specimens. These data provide evidence implicating CD4+ T-cell cytokines in the pathogenesis of RCDII. More broadly, they suggest that adaptive immune responses can contribute to innate IEL activation during mucosal inflammation.


2018 ◽  
Vol 50 (2) ◽  
pp. e231
Author(s):  
G. Losurdo ◽  
D. Piscitelli ◽  
F. Pezzuto ◽  
F. Fortarezza ◽  
C. Covelli ◽  
...  

2011 ◽  
Vol 14 (1) ◽  
pp. 127-133 ◽  
Author(s):  
K. Dudek ◽  
D. Bednarek

Cellular immune response of pigeons in the conditions of endotoxin fever and pyrogenic toleranceThe aim of this study was to investigate changes in selected parameters of cellular immune response in the conditions of endotoxin fever and pyrogenic tolerance in pigeons. On the first day of observation the experimental birds (n=18) were intravenously injected withEscherichia coliLPS at a dose of 10 μg/kg b.w., while the control animals (n=6) received apyrogenic physiological saline also in the form of injection. On the second and the third day of the experiment LPS was injected additionally at 24 h intervals. Four and a half hours after the saline and pyrogen administration blood samples were collected from the control and experimental pigeons. The following immunological assays were performed: WBC, leucogram and immunophenotyping of lymphocyte subsets in peripheral blood, i.e. CD 3+(T lymphocytes), CD 4+(T helper lymphocytes) and CD 8+(T suppressor/ cytotoxic lymphocytes) cells. In the conditions of endotoxin fever (i.e. after the first LPS injection) leucopenia, monocytopenia, heterophilia and eosinophilia were observed. Additionally, the immunophenotyping of peripheral blood lymphocytes indicated an increase in percentage of CD 3+, CD 4+and CD 8+cells in response to the single injection of LPS. In contrast, the consecutive injections of LPS, which created a pyrogenic tolerance effect, caused a decrease in WBC value, heteropenia, eosinopenia and lymphocytosis. Moreover, during this state an increase in percentage of CD 3+and CD 8+cells was demonstrated in contrast to the percentage of CD 4+lymphocytes. The general tendencies in cellular immune response of the affected pigeons in the conditions of endotoxin fever and pyrogenic tolerance aim at activation of defence mechanisms against LPS for its prompt elimination from the animal's organism.


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