Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study.

OBJECTIVE: To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. METHOD: A retrospective cross-sectional study, was conducted in a Tertiary hospital. PATIENTS: Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. INTERVENTION: The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. RESULTS: A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. CONCLUSION: Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.

Islet transplantation outcomes in type 1 diabetes and transplantation of HLA-DQ8/DR4: results of a single-centre retrospective cohort in Canada.

Background: In solid organ transplantation, HLA matching between donor and recipient is associated with superior outcomes. In islet transplantation, an intervention for Type 1 diabetes, HLA matching between donor and recipient is not performed as part of allocation. Susceptibility to Type 1 diabetes is associated with the presence of certain HLA types. This study was conducted to determine the impact of these susceptibility antigens on islet allograft survival. Methods: This is a single-centre retrospective cohort study. This cohort of transplant recipients (n = 268) received islets from 661 donor pancreases between March 11th, 1999 and August 29th, 2018 at the University of Alberta Hospital (Edmonton, AB, Canada). The frequency of the Type 1 diabetes susceptibility HLA antigens (HLA-A24, -B39, -DQ8, -DQ2 and-DQ2-DQA1∗05) in recipients and donors were determined. Recipient and donor HLA antigens were examined in relation to time to first C-peptide negative status/graft failure or last observation point. Taking into account multiple transplants per patient, we fitted a Gaussian frailty survival analysis model with baseline hazard function stratified by transplant number, adjusted for cumulative islet dose and other confounders. Findings: Across all transplants recipients of donors positive for HLA-DQ8 had significantly better graft survival (adjusted HRs 0.33 95% CI 0.17-0.66; p = 0.002). At first transplant only, donors positive for HLA-DQ2-DQA1∗05 had inferior graft survival (adjusted HR 1.96 95% CI 1.10-3.46); p = 0.02), although this was not significant in the frailty analysis taking multiple transplants into account (adjusted HR 1.46 95% CI 0.77-2.78; p = 0.25). Other HLA antigens were not associated with graft survival after adjustment for confounders. Interpretation: Our findings suggest islet transplantation from HLA-DQ8 donors is associated with superior graft outcomes. A donor positive for HLA-DQ2-DQA1∗05 at first transplant was associated with inferior graft survival but not when taking into account multiple transplants per recipient. The relevance of HLA-antigens on organ allocation needs further evaluation and inclusion in islet transplant registries and additional observational and interventional studies to evaluate the role of HLA-DQ8 in islet graft survival are required. Funding: None.

Modeling Peptide-Protein Interactions by a Logo-Based Method: Application in Peptide-HLA Binding Predictions.

Peptide-protein interactions form a cornerstone in molecular biology, governing cellular signaling, structure, and enzymatic activities in living organisms. Improving computational models and experimental techniques to describe and predict these interactions remains an ongoing area of research. Here, we present a computational method for peptide-protein interactions' description and prediction based on leveraged amino acid frequencies within specific binding cores. Utilizing normalized frequencies, we construct quantitative matrices (QMs), termed 'logo models' derived from sequence logos. The method was developed to predict peptide binding to HLA-DQ2.5 and HLA-DQ8.1 proteins associated with susceptibility to celiac disease. The models were validated by more than 17,000 peptides demonstrating their efficacy in discriminating between binding and non-binding peptides. The logo method could be applied to diverse peptide-protein interactions, offering a versatile tool for predictive analysis in molecular binding studies.

Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study

Abstract Objective To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. Method A retrospective cross-sectional study, was conducted in a Tertiary hospital. Patients Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. Intervention The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. Results A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. Conclusion Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.

The HLA-DQ8 transgenic mouse: A model to study the immune and cytotoxic responses to wheat gliadin.

A complete understanding of celiac disease (CD) pathogenesis has been hindered to date because of the lack of adequate in vivo models. Herein, we describe two in vivo approaches in HLA-DQ8-transgenic mice to study the intrinsic cytoxicity and immune features of wheat gliadin. By adopting the first method, we explored the mucosal architecture of the small intestine following the intra-gastric administration of wheat gliadin in mice treated with indomethacin, an inhibitor of cyclooxygenases. Mice showed a significant reduction of villus height, increased crypt depth and increased intraepithelial lymphocytes. The second approach involved the mucosal sensitization to gliadin via the intranasal route. This protocol induced a Th1/Th17 phenotype in mesenteric lymph nodes, as described in CD. In conclusion, these methods remain instrumental to analyze in vivo distinct biological features of wheat gliadin and related prolamins. Furthermore, the sensitization protocol could be exploited to test innovative strategies downregulating the gliadin-specific immunity.

Assessing the Prevalence of HLA-DQ2 and HLA-DQ8 in Lipedema Patients and the Potential Benefits of a Gluten-Free Diet.

Objective The aim of this study is to assess the prevalence of HLA-DQ2 and HLA-DQ8 in women diagnosed with lipedema. Methods Leukocyte histocompatibility antigen (HLA) tests of 95 women diagnosed with lipedema were analyzed using non-probabilistic sampling for convenience. The prevalence of HLA-DQ2 and HLA-DQ8 was compared to the general population. Results The prevalence of HLA-DQ2+ was 47.4%, that of HLA-DQ8+ was 22.2%, the presence of any celiac disease associated HLA (HLA-DQ2+ or HLA-DQ8+) was 61.1%, both HLA (HLA-DQ2+ and HLA-DQ8+) was 7.4%, and the absence of celiac disease associated HLA was 39%. Compared to the general population, there was a significantly higher prevalence of HLA-DQ2, HLA-DQ8, any HLA, and both HLAs in lipedema patients. The mean weight of patients with HLA-DQ2+ was significantly lower than the overall study population, and their mean BMI significantly differed from the overall mean BMI. Conclusion Lipedema patients seeking medical assistance have a higher prevalence of HLA-DQ2 and HLA-DQ8. Considering the role of gluten in inflammation, further research is needed to establish if this association supports the benefit of gluten withdrawal from the diet in managing lipedema symptoms.

The Second Highest Prevalence of Celiac Disease Worldwide: Genetic and Metabolic Insights in Southern Brazilian Mennonites.

Celiac disease (CD), despite its high morbidity, is an often-underdiagnosed autoimmune enteropathy. Using a modified version of the Brazilian questionnaire of the 2013 National Health Survey, we interviewed 604 Mennonites of Frisian/Flemish origin that have been isolated for 25 generations. A subgroup of 576 participants were screened for IgA autoantibodies in serum, and 391 participants were screened for HLA-DQ2.5/DQ8 subtypes. CD seroprevalence was 1:29 (3.48%, 95% CI = 2.16-5.27%) and biopsy-confirmed CD was 1:75 (1.32%, 95% CI = 0.57-2.59%), which is superior to the highest reported global prevalence (1:100). Half (10/21) of the patients did not suspect the disease. HLA-DQ2.5/DQ8 increased CD susceptibility (OR = 12.13 [95% CI = 1.56-94.20], p = 0.003). The HLA-DQ2.5 carrier frequency was higher in Mennonites than in Brazilians (p = 7 × 10-6). HLA-DQ8 but not HLA-DQ2.5 carrier frequency differed among settlements (p = 0.007) and was higher than in Belgians, a Mennonite ancestral population (p = 1.8 × 10-6), and higher than in Euro-Brazilians (p = 6.5 × 10-6). The glutathione pathway, which prevents reactive oxygen species-causing bowel damage, was altered within the metabolic profiles of untreated CD patients. Those with lower serological positivity clustered with controls presenting close relatives with CD or rheumatoid arthritis. In conclusion, Mennonites have a high CD prevalence with a strong genetic component and altered glutathione metabolism that calls for urgent action to alleviate the burden of comorbidities due to late diagnosis.

Meta-Analysis and Systematic Review of HLA DQ2/DQ8 in Adults with Celiac Disease.

Although people with human leukocyte antigens (HLA) DQ2 and/or DQ8 are more likely to develop celiac disease (CD), the condition cannot be fully explained by this genetic predisposition alone. Multiple, as yet unidentified, factors contribute to the genesis of CD, including genetics, the environment, and the immune system. In order to provide insight into a prospective possibility and an expanded screening technique, we aim to undertake a comprehensive and meta-analytical study of the assessment and distribution of HLA class II (HLA-DQ2/DQ8) in adult CD patients. A systematic review was conducted using an electronic search of databases (PubMed, Google Scholar, Embase, and Direct Science) from January 2004 to February 2022. DQ2/DQ2 homozygotes have the highest risk of developing CD. DQ2/DQ8 typing is an effective test to exclude CD from the differential diagnosis of a patient with CD symptoms. Although other non-HLA genes have been associated with CD, they are rarely considered at diagnosis because they account for only a small proportion of the heritability of CD. This finding, together with the information gathered previously, may be useful in considering widely available and economically feasible screening options for celiac disease in young people.

Celiac disease prevalence and predisposing-HLA in a cohort of 93 Williams-Beuren syndrome patients.

Williams-Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams-Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams-Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p > .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams-Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients.

Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach.

Human leukocyte antigens (HLAs) are pivotal in antigen processing, presenting to CD4+ T cells, and are linked to autoimmune disease susceptibility. In celiac disease, HLA-DQ2.5 and HLA-DQ8.1 bind gluten peptides on APCs, some recognized by CD4+ T cells, prompting inflammation and tissue damage. While extensively studied experimentally, these alleles lack comprehensive in silico analysis. To explore peptide-HLA preferences, we used molecular docking on peptide libraries, deriving quantitative matrices (QMs) for evaluating amino acids at nine-residue peptide binding cores. Our findings tie specific residue preferences to peptide backbone conformations. Validating QMs on known binders and non-binders showed strong predictive power (89-94% accuracy). These QMs excel in screening protein libraries, even whole proteomes, notably reducing time and costs for celiac disease risk assessment in novel proteins. This computational approach aligns with European Food Safety Authority guidance, promising efficient screening for potential celiac disease triggers.

Clinical presentation, biochemical profile, and HLA haplotype frequency of celiac disease among adults in Northwest China.

OBJECTIVE: To evaluate the clinical characteristics, biochemical parameters and the distribution of HLA-DQ genotypes among adult patients with celiac disease (CD) in Northwest China. METHODS: This cross-sectional study retrospectively collected clinical, biochemical, and HLA-DQ genotype of patients with CD from a tertiary hospital in Xinjiang Uygur Autonomous Region, China between March 2016 and December 2021. Small intestinal biopsy and serum-specific antibodies were used to diagnose CD. RESULTS: Of the 102 CD patients, 63.7% were women (female: male = 1.76:1), and the mean age was 47.3 ± 14.7 years at diagnosis. Common gastrointestinal symptoms included abdominal pain (50.0%), diarrhea (39.2%), and abdominal distension (24.5%). While common extraintestinal manifestations were anemia (48.0%), osteopenia or osteoporosis (36.3%), and fatigue (35.3%). Approximately 34.3% of patients with CD had comorbidities, with the most common being thyroid diseases (18.6%). Biochemical profiles showed lower hemoglobin, higher platelet count, and 25-hydroxyvitamin D (25[OH]D) deficiency. HLA-DQ2/DQ8 was detected among all 53 patients who underwent genotype testing; the frequency of the HLA-DQ2.5, DQ2.2, and DQ8 haplotypes was 71.7%, 24.5%, and 3.8%, respectively. CONCLUSIONS: CD was more common among women. Clinical manifestations include primarily gastrointestinal symptoms, but extraintestinal manifestations were not uncommon. Lower hemoglobin level, higher platelet count, and 25[OH]D deficiency are the main biochemical manifestations. The HLA-DQ2.5 and DQ2.2 haplotypes are the most common genotypes in CD.

Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700-0.7690) in comparison with 0.664 (95% CI: 0.632-0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.

Celiac disease may be rare among children in South China.

OBJECTIVE: The prevalence of celiac disease (CD) varies geographically and ethnically; however, the prevalence among children in South China remains unknown. We therefore determined the occurrence of CD among Chinese children in South China. METHODS: Serum samples were collected from children and assessed for anti-tissue transglutaminase IgA antibodies (anti-tTG-IgA) and total IgA. Anti-tTG-IgA+ participants underwent human leukocyte antigen (HLA) DQ2/DQ8 determination. Samples with serum total IgA <0.05 g/L were also analyzed for anti-tTG-IgG, and for HLA-DQ2/DQ8 if the values were above borderline. Participants who were anti-tTG-IgA/IgG+ and HLA-DQ2+ and/or HLA-DQ8+ underwent small bowel biopsy. RESULTS: A total of 8794 children were enrolled, of whom 479 had chronic unexplained abdominal symptoms. Three (0.034%) children were anti-tTG-IgA+ and ten (0.114%) had serum total IgA <0.05 g/L, all of whom were anti-tTG-IgG-. The three positive children were all HLA-DQ2+ and/or HLA-DQ8+. Two underwent gastroscopy, and histopathology of small intestinal biopsy showed duodenal villous blunting in one and increased intraepithelial lymphocytes in the other, neither consistent with a diagnosis of CD. CONCLUSION: Our study showed a prevalence of CD autoimmunity of 0.034% and failed to identify any cases of CD, suggesting a low prevalence of CD among children in South China.

Computational Alanine Scanning Reveals Common Features of TCR/pMHC Recognition in HLA-DQ8-Associated Celiac Disease.

In HLA-DQ8-associated celiac disease, Gliadin-γ1 or Gliadin-α1 peptide is presented to the cell surface and recognized by several types of T-cell receptor (TCR), but it is still unclear how the TCR, peptide, and the major histocompatibility complex (MHC) act together to trigger celiac disease. For now, most of the analysis is based on static crystal structures. And the detailed information about these structures based on energetic interaction is still lacking. Here, we took four types of celiac disease-related MHC-peptide-TCR structures from three patients to perform computational alanine scanning calculations using the molecular mechanics generalized born surface area (MM/GBSA) approach combined with a recently developed interaction entropy (IE) method to identify the key residues on TCR, peptide, and MHC. Our study aims to shed some light on the interaction mechanism of this complex protein interaction system. Based on detailed computational analysis and mutational calculations, important binding interactions in these triple-interaction complexes are analyzed, and critical residues responsible for TCR/pMHC recognition pattern in HLA-DQ8-associated celiac disease are presented. These detailed analysis and computational result should help shed light on our understanding of the celiac disease and the development of the medical treatment.

A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes.

To circumvent the limitations of available preclinical models for the study of type 1 diabetes (T1D), we developed a new humanized model, the YES-RIP-hB7.1 mouse. This mouse is deficient of murine major histocompatibility complex class I and class II, the murine insulin genes, and expresses as transgenes the HLA-A*02:01 allele, the diabetes high-susceptibility HLA-DQ8A and B alleles, the human insulin gene, and the human co-stimulatory molecule B7.1 in insulin-secreting cells. It develops spontaneous T1D along with CD4+ and CD8+ T-cell responses to human preproinsulin epitopes. Most of the responses identified in these mice were validated in T1D patients. This model is amenable to characterization of hPPI-specific epitopes involved in T1D and to the identification of factors that may trigger autoimmune response to insulin-secreting cells in human T1D. It will allow evaluating peptide-based immunotherapy that may directly apply to T1D in human and complete preclinical model availability to address the issue of clinical heterogeneity of human disease.

Transamidation Down-Regulates Intestinal Immunity of Recombinant α-Gliadin in HLA-DQ8 Transgenic Mice.

Enzymatic transamidation of gliadins by microbial transglutaminase (mTG) inhibits interferon-γ (IFN-γ) secretion by intestinal T cell lines in patients with celiac disease (CD). To gain insight into the cellular mechanisms underlying the down-regulatory effects of transamidation, we tested a single recombinant α-gliadin (r-gliadin) harbouring two immunodominant peptides, p13 (aa. 120-139) and p23 (aa. 220-239), in HLA-DQ8 transgenic mice, a model of gluten sensitivity. Mice were intranasally immunised with r-gliadin or r-gliadin transamidated by mTG (K-r-gliadin) along with cholera toxin, and the response of mesenteric lymph node cells was analysed by cytokine multiplex assay. An in vitro challenge with r-gliadin was characterised by secretion of specific cytokines featuring both innate immunity and the Th1/Th2/Th17 pattern of the adaptive response. Notably, transamidation specifically down-regulated the Th1 response. Structural studies performed on K-r-gliadin confirmed that specific glutamine residues in p13 and p23, previously found to be deamidated by tissue transglutaminase, were also transamidated by mTG. In silico analysis, simulating p13 and p23 peptide binding to HLA-DQ8 showed that these glutamines, in the form of glutamate, could interact by means of salt bridges with peculiar amino acids of the alpha chain of HLA-DQ8, suggesting that their transamidation may influence the HLA-restricted recognition of these peptides. Thus, the structural findings provided a rationale to explain the down-regulation of the r-gliadin-specific Th1 response following transamidation.

The frequency of HLA-DQ2/DQ8 haplotypes and celiac disease among the first-degree relatives of patients with celiac disease.

AIM: We evaluated the frequency of human leukocyte antigen (HLA) DQ2/DQ8 haplotypes as well as celiac disease (CD) among the first-degree relatives (FDRs) of CD patients, compared with healthy controls, and compared the HLA typing with serologic tests in this population. BACKGROUND: Until now, no study has examined the frequency of HLA-DQ2/DQ8 haplotypes among the FDRs of Iranian patients with CD. METHODS: In the current case-control study, 100 FDRs of CD patients and 151 healthy controls were included. Demographic characteristics were assessed using a research-made questionnaire. A blood sample was collected from each participant for HLA-DQ typing and measuring serum levels of anti-gliadin and anti-transglutaminase (anti-tTG) antibodies. RESULTS: The mean age of the FDRs of CD patients and controls was 30 and 35 years, respectively. Also, 51% (n=51) of the FDRs and 51.7% (n=78) of controls were female. CD was diagnosed among 3% (n=3) of the FDRs of CD patients. No significant difference was found in terms of the frequency of HLA-DQ alleles between the FDRs of CD patients and controls. Out of 100 FDRs of CD patients, 40% had HLA-DQ2 allele, 16% carried HLA-DQ8 allele, and 4% had both alleles. Surprisingly, the CD was diagnosed in three subjects among 60 FDRs of CD patients with HLA-DQ2 allele (3% of the whole population). This diagnosis was based on the results of serological tests as well as endoscopy and intestinal biopsy. CONCLUSION: CD was confirmed among 3% (n=3) of the FDRs of CD patients. We found that HLA typing is not effective in predicting CD among FDRs of CD patients. Other methods such as serological tests have a higher priority compared with HLA-DQ typing.

Retro-inverso D-peptides as a novel targeted immunotherapy for Type 1 diabetes.

Over the past four decades, the number of people with Type 1 Diabetes (T1D) has increased by 4% per year, making it an important public health challenge. Currently, no curative therapy exists for T1D and the only available treatment is insulin replacement. HLA-DQ8 has been shown to present antigenic islet peptides driving the activation of CD4+ T-cells in T1D patients. Specifically, the insulin peptide InsB:9-23 activates self-reactive CD4+ T-cells, causing pancreatic beta cell destruction. The aim of the current study was to identify retro-inverso-d-amino acid based peptides (RI-D-peptides) that can suppress T-cell activation by blocking the presentation of InsB:9-23 peptide within HLA-DQ8 pocket. We identified a RI-D-peptide (RI-EXT) that inhibited InsB:9-23 binding to recombinant HLA-DQ8 molecule, as well as its binding to DQ8 expressed on human B-cells. RI-EXT prevented T-cell activation in a cellular antigen presentation assay containing human DQ8 cells loaded with InsB:9-23 peptide and murine T-cells expressing a human T-cell receptor specific for the InsB:9-23-DQ8 complex. Moreover, RI-EXT blocked T-cell activation by InsB:9-23 in a humanized DQ8 mice both ex vivo and in vivo, as shown by decreased production of IL-2 and IFN-γ and reduced lymphocyte proliferation. Interestingly, RI-EXT also blocked lymphocyte activation and proliferation by InsB:9-23 in PBMCs isolated from recent onset DQ8-T1D patients. In summary, we discovered a RI-D-peptide that blocks InsB:9-23 binding to HLA-DQ8 and its presentation to T-cells in T1D. These findings set the stage for using our approach as a novel therapy for patients with T1D and potentially other autoimmune diseases.

Association Between Celiac Disease and Cancer.

Celiac disease (CD) is a chronic enteropathy that develops in genetically susceptible individuals after the ingestion of gluten. There has been a substantial increase in CD prevalence in the last 50 years, and it is now estimated that this disease affects approximately 1% of the population in the Western world. In the large majority of cases, CD is a benign disease, characterized by the complete resolution of symptoms and a normal life expectancy after the onset of a gluten-free diet (GFD). However, failure to adhere to a strict GFD bears the risk of adverse events and increases mortality. A considerable number of studies have considered the possible association between CD and neoplasms. In particular, an increased risk of malignancies, such as cancers of the gastrointestinal tract and intestinal lymphomas, has been reported. In this review, we summarize and discuss the current evidence on the possible association between CD and cancer.

[SUMMER-TYPE HYPERSENSITIVITY PNEUMONITIS CAUSED BY A HUMIDIFIER INDUCED IN SPRING, IN A 5-YEAR-OLD GIRL LIVING IN FUKUSHIMA-A CASE REPORT].

A 5-year-old girl living in Koriyama, Fukushima Prefecture was admitted in April with cough persisting for 1 month and fever. Chest X-ray showed diffuse ground-glass shadows in both lungs. After treatment with antibiotics, her fever went down on the 2nd day, and her cough subsided gradually. She was discharged on the 7th day, but her symptoms relapsed on the 8th day. Due to her worsening symptoms, she was readmitted on the 16th day. Chest CT scans showed enhancement of interstitial density. Serum anti-Trichosporon asahii antibody was positive. Her symptoms rapidly improved on a steroid regimen, and she was discharged on the 23th day. She was diagnosed as having summer-type hypersensitivity pneumonitis (SHP). She was instructed not to use a moldy humidifier and not to go to her grandmother's 57 years old wooden house. She has had no symptom after discharge. However, suspected mold was not found at her grandmother's house, and a provocation test there was negative. The HLA typing of the patient showed HLA-DQ8, which was previously described as SHP-sensitive.