Background. Celiac disease (CD) is a genetically determined immune-mediated disorder in which gluten immunogenic peptides are presented to CD4 T cells by HLA-DQ2.5, DQ8, DQ2.2, and their combinations. Our aim is to establish a risk gradient for celiac disease based on HLA-DQ profile in a brazilian representative population and the relevance of DQ2.2 in celiac disease development. Materials and Methods. 237 celiac patients and 237 controls (both groups with 164 females and 73 males) were included. All samples were tested for the presence of predisposing HLA-DQ alleles using the PCR-SSP method. Results were considered significant when p < 0.05. Disease risk was expressed as 1 : N for each HLA-DQ category described at this study. Results. DQ2.5 and/or DQ8 were detected in 224 celiac patients (94.5%) and 84 controls (35.4%). Eight celiac patients (3.4%) and 38 controls (16%) disclosed only DQ2.2. Even though DQ2.2 (β2/β2 or β2/x) showed a low CD risk of 1 : 251 and 1 : 550, respectively, the genotype DQ2.5/DQ2.2 (β2/β2) showed high CD risk of 1 : 10 (p < 0.0001). The disease risk gradient ranged from 1 : 3014 to 1 : 7. Conclusion. Our study allowed the determination of a risk gradient for celiac disease development in at-risk population, showing that DQ2.2 variant was relevant when associated with DQ2.5.
BackgroundAnacardium occidentale L phenolic lipid (LDT11) is used in traditional medicine as anti-inflammatory, astringent, antidiarrheal, anti-asthmatic and depurative. Phenolic derivatives, such as anacardic acid, extracted from cashew nut shell liquid (CNSL) have demonstrated biological and pharmacological properties, and its profile makes it a candidate for the development of new anti-inflammatory agents.The objective of the present study was to evaluate the anti-inflammatory profile of a derivative, synthesized from LDT11, on an in vitro cellular model.MethodsOrganic synthesis of the phenolic derivative of CNSL that results in the hemi-synthetic compound LDT11. The cytotoxicity of the planned compound, LDT11, was analyzed in murine macrophages cell line, RAW264.7. The cells were previously treated with LDT11, and then, the inflammation was stimulated with lipopolysaccharide (LPS), in intervals of 6 h and 24 h. The analysis of the gene expression of inflammatory markers (TNFα, iNOS, COX-2, NF-κB, IL-1β and IL-6), nitric oxide (NO) dosage, and cytokine IL-6 were realized.ResultsThe results showed that the phenolic derivative, LDT11, influenced the modulatory gene expression. The relative gene transcripts quantification demonstrated that the LDT11 disclosed an immunoprotective effect against inflammation by decreasing genes expression when compared with cells stimulated with LPS in the control group. The NO and IL-6 dosages confirmed the results found in gene expression.DiscussionThe present study evaluated the immunoprotective effect of LDT11. In addition to a significant reduction in the expression of inflammatory genes, LDT11 also had a faster and superior anti-inflammatory action than the commercial products, and its response was already evident in the test carried out six hours after the treatment of the cells.ConclusionThis study demonstrated LDT11 is potentially valuable as a rapid immunoprotective anti-inflammatory agent. Treatment with LDT11 decreased the gene expression of inflammatory markers, and the NO, and IL-6 production. When compared to commercial drugs, LDT11 showed a superior anti-inflammatory action.
BackgroundAlthough it is known that first degree relatives of celiac patients have an increased risk for celiac disease few studies are available on its incidence. We investigated the incidence of serologic conversion and of new cases of celiac disease among first degree relatives with negative results at a first screening.MethodsFrom a total of 634 first degree relatives of 186 biopsy-proven celiac disease patients diagnosed between October 2000 and October 2010, 450 subjects agreed to participate in the study (Group I), and underwent serologic screening. Between January 2010 and October 2012, out of the initial group of 450, 205 previously sero-negative subjects consented to participate in a second stage of the study and undergo new serologic testing (Group II). All serologically positive individuals of both groups (I and II) were genotyped for celiac disease-predisposing alleles (HLA-DQ2/DQ8).Results19 subjects (4.2%) out of the 450 subjects of Group I disclosed positive serologic results, presence of DQ2 and/or DQ8 alleles and celiac disease-compatible mucosal abnormalities. The 205 previously negative first degree relatives from Group II that underwent new serologic testing disclosed eight sero-converted subjects. Mucosal abnormalities in five of these patients confirmed the diagnosis of celiac disease. During the 10-year period of the study the incidence of sero-conversion was 8/205 and the incidence of biopsy-proven celiac disease cases was 5/205.ConclusionsOur data are coincident with other works on this subject and confirm once again that relatives of celiac patients, especially first degree relatives are at high risk of developing celiac disease. In view of the relatively low incidence further studies are needed to try to establish a useful and cost-effective algorithm for follow-up of relatives of celiac patients.
Results obtained by qPCR technique were highly reliable with no discordant results when compared with those obtained using PCR-SSP.
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