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This article reviews Celiac disease. It is believed that many people suffer from the disease which is the inability to absorb glutens from wheat and other grains. The only therapy is a gluten free diet but this does not work in 30 percent of patients. The pathogenesis of the disease is discussed. The disease will not develop unless a person has alleles that encode for HLA-DQ2 or HLA-DQ8 proteins. Environmental factors that have a role in the disease include feeding gluten before four months of age. Diagnosis, treatment and complications of the disease are presented.

We tested patients with celiac disease (CD) for the presence of serum anti-ganglioside antibodies. Six of twenty-seven patient sera were reactive against brain gangliosides by an agglutination immunoassay. Neurological examination in all six revealed the presence of distal sensory loss, consistent with the diagnosis of peripheral neuropathy. When tested by ELISA for antibodies to isolated GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides, all six were positive for IgG antibodies to at least one. The neuropathy of celiac disease may be autoimmune and associated with anti-ganglioside antibodies. The presence of IgG reactivity furthermore implicates a T cell-mediated response to ganglioside antigens. [Copyright &y& Elsevier]

P. H. R. Green and C. Cellier respond to a letter about their article "Celiac Disease" in the October 25, 2007 issue.

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INTRODUCTION: Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort. METHODS: We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18. RESULTS: We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82–3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36–2.12) over a follow-up of 8.8 years. DISCUSSION: Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Prevalence of Celiac Disease Among Children in Finland," by K. Mustalahti, J. Kokkonen et al. in the June 19, 2003 issue.

INTRODUCTION: Patients with celiac disease (CD) have an increased risk of encapsulated bacterial infections. Less is known about other serious infections in CD, especially in patients diagnosed in the 21st century. METHODS: We contacted all 28 pathology departments in Sweden through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort study and identified 20,088 individuals with CD (defined as villous atrophy) diagnosed in 2002–2017. Patients were matched for sex, age, and calendar year to 80,152 general population comparators and followed up until December 31, 2019. Serious infections were defined as having a hospital-based (inpatient and outpatient) diagnosis in the National Patient Register. Cox regression yielded adjusted hazard ratios (aHR) controlling for education, country of birth, and comorbidities. RESULTS: During 173,695 person-years of follow-up, 6,167 individuals with CD (35.5/1,000 person-years) had a serious infection. This was compared with 19,131 infections during 743,260 person-years (25.7/1,000 person-years) in matched comparators, corresponding to an aHR of 1.29 (95% confidence interval [CI] = 1.25–1.33). aHR were similar when restricted to infection requiring hospital admission (1.23; 95% CI = 1.17–1.29). The excess risk of serious infections also persisted beyond the first year after CD diagnosis (aHR = 1.24; 95% CI = 1.20–1.29). Patients with CD were at risk of sepsis (aHR = 1.26; 95% CI = 1.09–1.45) and gastrointestinal infections (1.60; 95% CI = 1.47–1.74). Mucosal healing during CD follow-up did not influence the risk of subsequent serious infections. DISCUSSION: This nationwide study of patients with celiac disease diagnosed in the 21st century revealed a significantly increased risk of serious infections. While absolute risks were modest, vaccinations should be considered during CD follow-up care. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To determine the risk of inflammatory bowel disease (IBD) in patients with celiac disease (CeD) (and vice versa) compared with general-population comparators. METHODS: Using Swedish histopathology and healthcare register data, we identified 48,551 patients with CeD and 83,529 with IBD diagnosed in 1969–2016. Each patient was compared with age- and sex-matched general-population comparators (CeD: n = 240,136; IBD: n = 408,195). Cox regression estimated hazard ratios (HRs) for IBD in patients with CeD and vice versa. Our main analyses were limited to events beyond the first year of follow-up to reduce potential surveillance bias. RESULTS: During follow-up, 784 (1.6%) patients with CeD were diagnosed with IBD compared with 1,015 (0.4%) matched comparators. In patients with CeD, the HR for IBD was 3.91 (95% confidence interval [CI] 3.56–4.31), with largely similar HRs for Crohn's disease (4.36; 3.72–5.11) and ulcerative colitis (3.40; 3.00–3.85). During follow-up, 644 (0.8%) patients with IBD and 597 (0.1%) comparators were diagnosed with CeD. The HR for CeD in patients with IBD was 5.49 (95% CI 4.90–6.16), with the highest risk estimates seen in ulcerative colitis (HR = 6.99; 6.07–8.05), and the HR for Crohn's disease was 3.31 (2.69–4.06). In patients with CeD and IBD, the diagnostic interval was usually <1 year; however, HRs of 3–4 were seen even after 10 years of follow-up. During 20 years of follow-up, 2.5% of patients with CeD developed incident IBD, and 1.3% of patients with IBD developed CeD. DISCUSSION: The bidirectional association between CeD diagnosis and IBD warrants attention in the initial assessment and follow-up of these conditions. Their co-occurrence, independent of temporal sequence, suggests shared etiology. [ABSTRACT FROM AUTHOR]

Replies to comments on an article on the spectrum of symptoms of cryptosporidiosis, published in a previous issue of 'The American Journal of Medicine.'

Celiac disease (CeD) has been linked to an increased risk of other autoimmune diseases, yet the impact of delayed CeD diagnosis on risk of developing additional autoimmune diseases remains uncertain. We investigated this through a nationwide matched case-control study. Using the ESPRESSO cohort with histophatology data from Sweden's 28 pathology departments, we assessed 46,575 biopsy-confirmed CeD cases from 1964 to 2017. We extracted 225,295 matched controls without histopathology information from the Swedish Total Population Register. Autoimmune disease was defined through diagnostic codes in the National Patient Register. Through conditional logistic regression we estimated odds ratio (OR) of autoimmune disease up until CeD diagnosis/matching date comparing CeD cases to controls across different age strata. A total of 3059 (6.6 %) CeD patients and 4076 (1.8 %) controls had earlier autoimmune disease. The overall OR for autoimmune disease in CeD was 3.50 (95%CI 3.32–3.70). The risk of autoimmune disease did not escalate with increasing age at CeD diagnosis. Compared with controls, the OR of autoimmune disease in CeD patients was 7.70 (95%CI 4.71–12.57) in those diagnosed with CeD in 0–4 years, 19.02 (95%CI 13.80–26.23) in 5–9 years, 6.18 (95%CI 5.14–7.44) in 10–14 years, 4.80 (95%CI 3.97–5.79) in 15–19 years, 4.24 (95%CI 3.55–5.07) in 20–29 years, 4.65 (95%CI 3.93–5.51) in 30–39 years, 3.67 (95%CI 3.30–4.09) in 40–59 years, and 1.67 (95%CI 1.50–1.85) in ≥60 years. This study revealed an increased risk of autoimmune disease among CeD patients compared with controls. However, older age at CeD diagnosis did not seem to escalate the risk of autoimmune diseases. • The diagnosis of celiac disease peaked at age 2 and subsequently declined as age progresses. • Celiac disease patients exhibited a higher prevalence of autoimmune diseases compared to their controls. • The risk of autoimmune disease did not escalate with increasing age at the celiac disease diagnosis. [ABSTRACT FROM AUTHOR]

Background: Celiac disease has been associated with hyposplenism, and multiple case reports link celiac disease and pneumococcal infections; however, increased risk of pneumococcal infection in celiac disease has not been confirmed. The purpose of this study was to conduct a systematic review to determine the risk of pneumococcal infections in celiac disease.Methods: Relevant studies were identified using electronic bibliographic searches of PubMed, OVID, Medline, and EMBASE (1980 to February 2017) and reviewing abstracts from major conferences in gastroenterology. Using number of events in celiac patients and referent patients, we calculated a summary relative risk of pneumococcal infections. All analyses were conducted in Comprehensive Meta-Analysis software using random-effects assumptions.Results: Of a total of 156 articles, 3, representing 3 large databases (the Swedish National Inpatient Register; the Oxford Record Linkage Study; and the English National Hospital Episode Statistics) were included. Each compared patients with celiac disease and confirmed pneumococcal infection to a specific reference group: inpatients and/or the general population. Overall, the odds of pneumococcal infection were higher among hospitalized celiac patients compared with controls (odds ratio 1.66; 95% confidence interval 1.43-1.92). There was no evidence of heterogeneity (Q[1] = 1.17, P = .56, I2 = 0%).Conclusions: Celiac disease is associated with an increased risk of pneumococcal infection. Preventive pneumococcal vaccination should be considered for those with celiac disease, with special attention to those aged 15-64 years who have not received the scheduled pneumococcal vaccination series as a child. [ABSTRACT FROM AUTHOR]

Background: Several screening studies have indicated an increased prevalence of celiac disease (CD) among individuals with autoimmune thyroid disease (ATD), but estimates have varied substantially. Objective: The aim of this study was to examine the prevalence of CD in patients with ATD. Method: A systematic review was conducted of articles published in PubMed Medline or EMBASE until September 2015. Non-English papers with English-language abstracts were also included, as were research abstracts without full text available when relevant data were included in the abstract. Search terms included 'celiac disease' combined with 'hypothyroidism' or 'hyperthyroidism' or 'thyroid disease.' Fixed-effects inverse variance-weighted models were used. Meta-regression was used to examine heterogeneity in subgroups. Results: A pooled analysis, based on 6024 ATD patients, found a prevalence of biopsy-confirmed CD of 1.6% [confidence interval (CI) 1.3-1.9%]. Heterogeneity was large (I2 = 70.7%). The prevalence was higher in children with ATD (6.2% [CI 4.0-8.4%]) than it was in adults (2.7%) or in studies examining both adults and children (1.0%). CD was also more prevalent in hyperthyroidism (2.6% [CI 0.7-4.4%]) than it was in hypothyroidism (1.4% [CI 1.0-1.9%]). Conclusions: About 1/62 patients with ATD have biopsy-verified CD. It is argued that patients with ATD should be screened for CD, given this increased prevalence. [ABSTRACT FROM AUTHOR]

Background and Aims Patients with celiac disease (CD) are reported to be at increased risk for headaches, though large studies are lacking. We aimed to examine the risk of headache-related healthcare encounters in patients with CD in a nationwide population-based setting. Methods In this population-based retrospective cohort study, we searched all (n = 28) pathology departments in Sweden and identified patients with CD based on the presence of villous atrophy (VA). Each patient was matched to up to 5 controls, by age, gender, calendar period, and region. Using Cox proportional hazards, we tested for an association between CD and subsequent headache-related visit. We also tested this association for those with intestinal inflammation but normal villi, and subjects with positive CD serologies but normal histology. Results Among 28,638 patients with CD and 143,126 controls, headache-related visit occurred in 1,337 (4.7%) and 4,102 (2.9%), respectively. The incidence of headache-related visit was 423 per 100,000 person-years in CD patients and 254 per 100,000 person-years in controls (HR 1.66; 95% CI 1.56-1.77; P < .0001). Individuals having inflammation without VA on small intestinal biopsy (n = 12,898; HR 2.08; 95% CI 1.90-2.27; P < .0001) and those with normal mucosa but positive CD serology (n = 3,617; HR 1.83; 95% CI 1.57-2.12; P < .0001) were also at increased risk for headache-related visit. Conclusions In this population-based study we found a significantly increased risk of headache-related visits in patients with CD; this increase was also present in patients with intestinal inflammation and those with positive CD serology but with normal mucosal architecture on small bowel biopsy. Though limited by surveillance bias, this study indicates that headache-related visits are more common in these populations. [ABSTRACT FROM AUTHOR]

Background & Aims Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Methods Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. Results During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0–3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3–9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5–50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0–5.9). Conclusion Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. [ABSTRACT FROM AUTHOR]

Background: As measured from videocapsule endoscopy images, the small intestinal mucosa of untreated celiac patients has significantly greater and more varied texture compared to normal patients. Three-dimensional modeling using shape-from-shading principles may further increase classification accuracy. Methods: A sequence of 200 consecutive videocapsule images acquired at a 2s–1 frame rate and 576×576 pixel dimension, were obtained at four locations in the small intestinal lumen of ten patients with biopsy-proven celiac disease and ten control patients. Each two-dimensional image was converted to a three-dimensional architectural approximation by considering the 256 grayscale level to be linearly representative of image depth. From the resulting three-dimensional architecture, distinct luminal protrusions, representative of the macro-architecture, were automatically identified by computer algorithm. The range and number of protrusions per image, and their width and height, were determined for celiacs versus controls and tabulated as mean±SD. Results: The mean number of villous protrusions per image was 402.2±15.0 in celiacs versus 420.8±24.0 in controls (p <0.001). The average protrusion width was 14.7 pixels in celiacs versus 13.9 pixels in controls (p =0.01). The mean protrusion height was 3.10±2.34 grayscale levels for celiacs versus 2.70±0.43 grayscale levels for controls (p <0.001). Thus celiac patients had significantly fewer protrusions on the luminal surface of the small intestine as compared with controls, and these protrusions had greater dimensions, suggesting they are indicative of a mosaic (cobblestone) macro-architectural pattern which is common in celiacs. Conclusions: Shape-from-shading modeling is useful to explore luminal macro-architecture and to detect significant differences in luminal morphology in celiac versus normal patients, which can increase the usefulness of videocapsule studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Videocapsule endoscopy can be useful to detect small intestinal pathology in celiac disease patients. However, presence of extraneous features including air bubbles and opaque fluids can complicate the analysis. A technique for quantitative analysis of videocapsule images is presented that is robust to presence of extraneous features. Method: Videocapsule clips were acquired from five small intestinal locations in 12 celiacs with villous atrophy and 11 control patients. Clips were 200 frames in length, their resolution was 576×576 pixels and 256 grayscale levels, with 2/s frame rate. The dominant period (DP), defined as the tallest peak in the ensemble average power spectrum, was computed over each clip without removal of extraneous features. Ensemble average basis images were constructed, and measurements were made of their frame-to-frame variation in brightness and texture. Results: From pooled basis images, celiac images had greater texture than controls and exhibited more brightness variation (p <0.05 in mean and p <0.01 in standard deviation). In celiacs, correlation existed between greater textural alterations versus longer DP (r 2 =0.47), and between greater brightness variation and longer DP (r 2 =0.33). There was no significant correlation between quantitative features and DP in controls (r 2 <0.25). Conclusions: Using this new method, celiac videoclips were quantitatively distinguishable from control videoclips without manual or computer-assisted detection, masking, and removal of extraneous image features. Furthermore, in celiac but not control basis images, larger textural and brightness alterations were correlated to longer DP. Greater textural and brightness alterations, and thus longer periodicities, are likely related to presence of villous atrophy. [Copyright &y& Elsevier]

Abstract: Background: Although videocapsule endoscopy images are helpful in the evaluation of celiac disease, their interpretation is subjective. Quantitative disease markers could assist in determining the extent of villous atrophy and response to treatment. Method: Capsule endoscopy images were acquired from celiac patients with small bowel pathology (N =11) and from control patients (N =10). Image resolution was 576×576 pixels in dimension, 256 grayscale levels, and had a 2s−1 frame rate. Pixel brightness and image texture were measured over 10×10 pixel subimages and then averaged for 56×56 subimages per frame. Measurements were obtained at five locations from proximal to distal small intestine in each patient. At each location, measurements were calculated using 200 consecutive image frames (100s). Mean frame-to-frame pixel brightness, image texture, and periodicity in brightness, an estimate of wall motion or intestinal motility, were computed and used for classification with a nonlinear discriminant function. Results: From pooled data, celiac images had greater texture than did images from control patients (p <0.001) and exhibited more frame-to-frame brightness variation as well (p =0.032). The dominant period of brightness was longer in celiacs (p =0.001), possibly indicating decreased motility. Using the markers for three-dimensional nonlinear classification of celiacs versus controls, sensitivity was 92.7% and specificity was 93.5%. The relationship between dominant period and small intestinal transit time was approximately linear for both celiacs and controls (r 2 =0.42 and r 2 =0.55, respectively). Conclusions: Videocapsule images can be quantified to detect villous atrophy throughout the small intestine, and to distinguish individuals with celiac disease from individuals lacking mucosal atrophy. [ABSTRACT FROM AUTHOR]

Abstract: A link between celiac disease and schizophrenia has been postulated for several years, based primarily on reports of elevated levels of antibody to gliadin in patients. We sought to examine the proposed connection between schizophrenia and celiac disease by characterizing the molecular specificity and mechanism of the anti-gliadin immune response in a subset of individuals with schizophrenia. Blood samples from individuals with schizophrenia and elevated anti-gliadin antibody titer were examined for celiac disease-associated biomarkers, including antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antibody did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients. Further characterization and understanding of the immune response to gluten in schizophrenia may provide novel insights into the etiopathogenesis of specific disease phenotypes. [Copyright &y& Elsevier]

Abstract: Celiac disease (CD) is an autoimmune disorder that is triggered by an immune response to gluten in genetically predisposed individuals. Although considered a primary gastrointestinal disease, CD is now known to have widespread systemic manifestations. We attempted to define the nature and role of systemic cytokine levels in the pathophysiology of CD. Multiplex cytokine assays were performed on four different groups of adult patients; patients with active CD (ACD), patients on a gluten-free diet (GFD) with positive TTG IgA antibodies, patients on a GFD with negative antibodies, and those with refractory CD (RCD). The results were compared with values in healthy adult controls. Patients with active CD and those on GFD with positive antibodies had significantly higher levels of proinflammatory cytokines, such as interferon-γ, interleukin (IL)–1β, tumor necrosis factor–α, IL-6 and IL-8, and also Th-2 cytokines such as IL-4 and IL-10, compared with normal controls and patients on GFD without antibodies. Interestingly patients on GFD for less than 1 year had significantly higher levels of both proinflammatory cytokines and Th2 cytokines compared with the patients on GFD for more than 1 year. In addition, a statistically significant correlation between levels of TTG IgA titers and serum levels of Th-2 cytokines IL-4 (p < 0.001), IL-10 (p < 0.001) and inflammatory cytokines such as IL-1α (p < 0.001), IL-1β (p < 0.005), and IL-8 (p < 0.05) was observed. [Copyright &y& Elsevier]

Abstract: Purpose: Celiac disease is associated with hypocholesterolemia, which is thought to contribute to a favorable cardiovascular risk profile. This led to suggestions that the diagnosis of celiac disease and its treatment with a gluten-free diet may result in elevation of the serum cholesterol level and worsen this risk profile. However, no study proves this in adults. We therefore examined the effect of a gluten-free diet on the lipid profile in patients with celiac disease. Subjects and methods: We identified 132 patients with celiac disease who adhered to a gluten-free diet and had lipid profiles performed before and after a median of 20.5 months on the diet. The patients lacked diseases that may affect serum lipids. Results: There were significant increases in total cholesterol and high-density lipoprotein (HDL) cholesterol (P < .0001) but not low-density lipoprotein (LDL) cholesterol (P =.06). The LDL/HDL ratio decreased by 0.36±0.7 (P < .0001). Both men and women had a significant increase in total cholesterol and HDL and a significant decrease in the LDL/HDL ratio. Only men had increases in LDL (P =.02). The greatest increase in lipid values was seen in those with the lowest initial values. The largest increase in HDL was seen in subjects with more severe disease as indicated by low albumin level and presence of total villous atrophy. Conclusions: Diagnosis of celiac disease and its treatment with a gluten-free diet resulted in improvement in the lipoprotein profile, which included an increase in HDL and a decrease in the LDL/HDL ratio. [Copyright &y& Elsevier]

Summary Tissue-resident lymphocytes play a key role in immune surveillance, but it remains unclear how these inherently stable cell populations respond to chronic inflammation. In the setting of celiac disease (CeD), where exposure to dietary antigen can be controlled, gluten-induced inflammation triggered a profound depletion of naturally occurring Vγ4+/Vδ1+ intraepithelial lymphocytes (IELs) with innate cytolytic properties and specificity for the butyrophilin-like (BTNL) molecules BTNL3/BTNL8. Creation of a new niche with reduced expression of BTNL8 and loss of Vγ4+/Vδ1+ IELs was accompanied by the expansion of gluten-sensitive, interferon-γ-producing Vδ1+ IELs bearing T cell receptors (TCRs) with a shared non-germline-encoded motif that failed to recognize BTNL3/BTNL8. Exclusion of dietary gluten restored BTNL8 expression but was insufficient to reconstitute the physiological Vγ4+/Vδ1+ subset among TCRγδ+ IELs. Collectively, these data show that chronic inflammation permanently reconfigures the tissue-resident TCRγδ+ IEL compartment in CeD. Video Abstract Graphical Abstract Highlights • Innate-like Vδ1+ IELs are superseded by interferon-γ-producing Vδ1+ IELs in CeD • The Vδ1+ IEL TCR repertoire is permanently reshaped in CeD • A molecular signature defines Vδ1+ IEL expansions in active CeD • Loss of BTNL8 expression coincides with permanent loss of BTNL3/8-reactive γδ+ IELs in CeD Chronic inflammation, driven in the context of celiac disease by persistent antigenic challenge with dietary gluten, permanently reshapes the tissue-resident innate-like TCRγδ+ intraepithelial lymphocyte compartment. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Screening studies have revealed that celiac disease is common in the United States; however, there are scant data on the mode of presentation. We analyzed the trends in clinical presentation over the last 52 years in a large cohort of biopsy-proven patients seen in 1 center. Subjects and methods: Patients (n = 590) were divided into 6 groups based on the year of diagnosis (1952-2004). Groups were compared for trends in age at diagnosis, childhood diagnosis, duration of symptoms, mode of presentation (diarrhea, bone disease, anemia, incidental at esophagogastroduodenoscopy, screening), and presence of malignancy. Results: Diagnosis was at an older age since 1980 (P = .007), and there was a significant negative linear trend in patients presenting with diarrhea (P<.001) over time and a positive linear trend in asymptomatic patients detected on screening (P<.001). There was a significant negative linear trend in patients with a malignancy (P = .02) and duration of symptoms before diagnosis of celiac disease (P = .001), although only the subgroup without diarrhea had improvement in delay of diagnosis of celiac disease (assessed by a shorter duration of symptoms) (P = .05). Comparison of patients with and without diarrhea showed no significant difference in age (42.9 years vs 43.7 years, P = .59), gender (29.3% M vs 34.6%, P = .59), and presence of childhood disease (8.0% vs 9.8%, P = .43) or malignancies (9.8% vs 8.9%, P = .71). Conclusion: There is a trend toward fewer patients presenting with symptomatic celiac disease characterized by diarrhea and a significant shift toward more patients presenting as asymptomatic adults detected at screening. [Copyright &y& Elsevier]