Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD.
Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease.
Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms.
Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

OBJECTIVE: Autoantibodies against tissue transglutaminase (tTG) are serological markers of celiac disease. The aim was to study the applicability of human leukocyte antigen (HLA)-genotyping and tTG autoantibodies in the screening of celiac disease in a longitudinal birth cohort followed to age 15 years.
METHODS: Included were 13,860 HLA-DQ-genotyped children at birth and previously invited to a screening at age 3 and 9 years, respectively. HLA-DQB1*02 and/or DQB1*03:02 (HLA-risk) children were compared with non-HLA-DQB1*02 and non-DQB1*03:02 (HLA-nonrisk) children. The present study reinvited 12,948/13,860 (93.4%) children at age 15 years of whom 1056/2374 (44.5%) participated in screening at both age 3 and 9 years. Both immunoglobulin A (IgA) and G (IgG) autoantibodies against tTG were analyzed separately in radiobinding assays. Persistently tTG autoantibody-positive children were examined with intestinal biopsy to confirm the diagnosis of celiac disease.
RESULTS: At age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA-risk children compared with 0/1824 HLA-nonrisk children (p < 0.001). By age 9 years, celiac disease was diagnosed in 72/1910 (3.8%) HLA-risk children compared with 0/2167 HLA-nonrisk children (p < 0.001). Screening at age 15 years detected 14/1071 (1.3%) HLA-risk children positive for IgA-tTG and/or IgG-tTG of whom 12/1071 (1.1%) remained persistently positive. Among those, 10/1071 (0.9%, 95% confidence interval: 0.4%-1.7%) HLA-risk children were diagnosed with celiac disease compared with 0/1303 HLA-nonrisk children (p < 0.001) and 5/491 (1.0%) were negative in screenings at both 3 and 9 years of age.
CONCLUSIONS: Screening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA-risk.

OBJECTIVE: While European Society of Pediatric Gastroenterology Hepatology and Nutrition advocates a no-biopsy pathway for the diagnosis of celiac disease (CeD) in children if IgA anti-tissue transglutaminase antibody (anti-tTG ab) titer is ≥10-fold upper limit of normal (ULN) and have a positive IgA anti-endomysial antibody (EMA); the data for anti-tTG Ab titer-based diagnosis of CeD in adults is still emerging. We planned to validate if IgA anti-tTG Ab titer ≥10-fold predicts villous abnormalities of modified Marsh grade ≥2 in Asian adult patients with CeD.
METHODS: We recruited 937 adult patients with positive anti-tTG Ab from two databases, including AIIMS Celiac Clinic and Indian National Biorepository. The diagnosis of definite CeD was made on the basis of a positive anti-tTG Ab and the presence of villous abnormalities of modified Marsh grade ≥2.
RESULTS: Of 937 adult patients with positive anti-tTG Ab, 889 (91.2%) showed villous abnormalities of modified Marsh grade ≥2. Only 47.6% of 889 adults with CeD had anti- tTG Ab titers of ≥10-fold. The positive predictive value (PPV) and specificity of anti tTG Ab titer ≥10-fold for predicting modified Marsh grade ≥2 were 99.8% and 98%, respectively. At anti-tTG Ab titer ≥11-fold, specificity and PPV were 100% for predicting villous abnormalities of modified Marsh grade ≥2.
CONCLUSIONS: Approximately 50% of adults with CeD may benefit from the no biopsy pathway, reducing the health burden and risks of gastroscopy/anesthesia.

OBJECTIVE: Celiac disease (CD) is an autoimmune enteropathy that develops in genetically susceptible individuals. The typical gastrointestinal manifestation is diarrhea but symptoms of dyspepsia, such as epigastric pain, nausea, or satiety, can sometimes appear. Previous studies have reported that the prevalence of CD in patients with dyspepsia can be as high as 7%. The aim of the present study was to evaluate CD seroprevalence in subjects with dyspeptic symptoms and a control group in a Mexican population.
METHODS: A case-control study was conducted on blood donors that answered the PAGI-SYM questionnaire for dyspepsia and in whom IgA antibodies to tissue transglutaminase 2 (IgA anti-tTG2) and IgG antibodies to deamidated gliadin peptide (IgG anti-DGP) were determined. CD seroprevalence in subjects with dyspeptic symptoms and in asymptomatic subjects was compared.
RESULTS: A total of 427 subjects (76.3% men), with a mean patient age of 34 years (range of 18-65 years) were included. Of those participants, 87 (20.3%) had symptoms of dyspepsia (group A) and 340 (79.6%) were asymptomatic (group B). Antibodies were positive in one (1.15%) of the group A subjects (1/87, 95% CI 0.2-6 %), whereas they were positive in 4 (1.18%) of the group B subjects (4/340, 95% CI 0.4-2.9%, p = 0.59).
CONCLUSIONS: CD seroprevalence in the study population with dyspeptic symptoms (1%) was not different from that of the control population. Thus, CD screening in Mexican patients with dyspepsia is not justified.

Tissue transglutaminase (TG2) expressed in monocytes and macrophage is known to participate in processes during either early and resolution stages of inflammation. The alternative splicing of tissue transglutaminase gene is a mechanism that increases its functional diversity. Four spliced variants are known with truncated C-terminal domains (TGM2_v2, TGM2_v3, TGM2_v4a, TGM2_v4b) but scarce information is available about its expression in human monocyte and macrophages. We studied the expression of canonical TG2 (TGM2_v1) and its short spliced variants by RT-PCR during differentiation of TPH-1 derived macrophages (dTHP-1) using two protocols (condition I and II) that differ in Phorbol-12-myristate-13-acetate dose and time schedule. The production of TNF-α and IL-1β in supernatant of dTHP-1, measured by ELISA in supernatants showed higher proinflammatory milieu in condition I. We found that the expression of all mRNA TG2 spliced variants were up-regulated during macrophage differentiation and after IFN-γ treatment of dTHP-1 cells in both conditions. Nevertheless, the relative fold increase or TGM2_v3 in relation with TGM2_v1 was higher only with the condition I. M1/M2-like THP-1 macrophages obtained with IFN-γ/IL-4 treatments showed that the up-regulation of TGM2_v1 induced by IL-4 was higher in relation with any short spliced variants. The qualitative profile of relative contribution of spliced variants in M1/M2-like THP-1 cells showed a trend to higher expression of TGM2_v3 in the inflammatory functional phenotype. Our results contribute to the knowledge about TG2 spliced variants in the biology of monocyte/macrophage cells and show how the differentiation conditions can alter their expression and cell function.

BACKGROUND: The prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1-7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers.
METHODS: Serum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher\'s exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated.
RESULTS: 808 JIA cases and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs. 68% p = 0.309). A total of 1.2% of cases were IgA deficient compared to none of the controls (p = 0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA ≥ 4u/mL compared to 3.6% of controls (p = 0.216) (OR = 0.5; 95% C.I = 0.1-1.4); and 0.8% of cases had tTG IgA > 10u/mL compared to 1.4% of controls (p = 0.627) (OR = 0.5; 95%C.I = 0.1-2.9).
CONCLUSIONS: Using the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for CD.

High gluten intake is associated with increased risk of celiac disease (CD) in children at genetic risk.
We aimed to investigate if different dietary gluten sources up to age 2 y confer different risks of celiac disease autoimmunity (CDA) and CD in children at genetic risk.
Three-day food records were collected at ages 6, 9, 12, 18, and 24 mo from 2088 Swedish genetically at-risk children participating in a 15-y follow-up cohort study on type 1 diabetes and CD. Screening for CD was performed with tissue transglutaminase autoantibodies (tTGA). The primary outcome was CDA, defined as persistent tTGA positivity. The secondary outcome was CD, defined as having a biopsy specimen showing Marsh score ≥ 2 or an averaged tTGA level ≥ 100 Units. Cox regression adjusted for total gluten intake estimated HRs with 95% CIs for daily intake of gluten sources.
During follow-up, 487 (23.3%) children developed CDA and 242 (11.6%) developed CD. Daily intake of ≤158 g porridge at age 9 mo was associated with increased risk of CDA (HR: 1.53; 95% CI: 1.05, 2.23; P = 0.026) compared with no intake. A high daily bread intake (>18.3 g) at age 12 mo was associated with increased risk of both CDA (HR: 1.47; 95% CI: 1.05, 2.05; P = 0.023) and CD (HR: 1.79; 95% CI: 1.10, 2.91; P = 0.019) compared with no intake. At age 18 mo, milk cereal drink was associated with an increased risk of CD (HR: 1.16; 95% CI: 1.00, 1.33; P = 0.047) per 200-g/d increased intake. No association was found for other gluten sources up to age 24 mo and risk of CDA or CD.
High daily intakes of bread at age 12 mo and of milk cereal drink during the second year of life are associated with increased risk of both CDA and CD in genetically at-risk children.

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