Study of the immune response in celiac patients with selective IgA deficiency who start a gluten-free diet.

Studies are scarce regarding IgG anti-tissue transglutaminase 2 (tTG) normalization in selective IgA deficient (SIgAD) celiac disease (CD) patients after beginning a gluten free diet (GFD). The aim of this study is to analyse the decreasing dynamics of IgG anti-tTG in patients diagnosed with CD who start a GFD. To achieve this objective, IgG and IgA anti-tTG levels at diagnosis and during follow-up in 11 SIgAD CD patients and in 20 IgA competent CD patients were retrospectively evaluated. At diagnosis, statistical differences were not found when comparing IgA anti-tTG levels of IgA competent subjects with IgG anti-tTG levels of SIgAD subjects. Regarding the decreasing dynamics, even though no statistical differences were found (p = 0.06), normalization rates were slower for SIgAD CD patients. After 1 and 2 years on GFD, respectively, only 18.2% and 36.3% of the SIgAD CD patients normalized IgG anti-tTG levels; otherwise, IgA anti-tTG reached values under the reference values in 30% and 80% of the IgA competent patients in the same time-points. Although IgG anti-tTG has demonstrated a high diagnostic efficiency in SIgAD CD pediatric patients, this test does not appear to be as precise for long-term GFD response monitoring as IgA anti-tTG levels in IgA sufficient patients.

Efficacy Study of Anti-Endomysium Antibodies for Celiac Disease Diagnosis: A Retrospective Study in a Spanish Pediatric Population.

The aim of this study was to assess the efficacy of anti-endomysium antibodies (EMA) as a serological marker for celiac disease (CD) diagnosis in a pediatric population. A retrospective study of pediatric patients who underwent a CD serological markers study: EMA and anti-tissue transglutaminase antibodies (anti-TG2). Clinical symptomatology, degree of histological lesion, human leukocyte antigen (HLA) haplotype compatible with CD (HLA DQ2 and/or DQ8), and final diagnosis were taken into account. We included 445 patients who were classified in two groups according to the final diagnosis. Group 1: 232 children with CD, 91.4% of whom exhibited small intestinal villous atrophy, 228 being EMA-positive and four EMA-negative. Group 2: 213 children with a non-CD diagnosis, 212 EMA negative and one EMA positive. Both antibodies, EMA and anti-TG2, reached similar sensitivities, 98% and 99% respectively, while EMA had a higher specificity (99%) than anti-TG2 (93%). By using both markers combined, compared to using anti-TG2 alone, 5.7% of patients are better diagnosed. However, when we compare the efficacy of EMA and anti-TG2 in asymptomatic and symptomatic patients, the sensitivity of EMA is 98% irrespective of symptoms, thus higher than for anti-TG2 ≥10 × upper limit of normal (ULN) (respectively 77% and 84%). Our results support the use of EMA to increase CD diagnostic accuracy in a non-biopsy approach, especially in asymptomatic children.

Prevalence of celiac disease serological markers in a cohort of Italian rheumatological patients.

AIM: To assess the prevalence of celiac disease (CD) serological markers in a cohort of patients referred to an Italian rheumatological outpatient clinic. BACKGROUND: Current guidelines do not suggest CD screening in patients with rheumatological diseases and these subjects are not considered to be at high risk for CD. METHODS: A total of 230 sera of rheumatological patients referred to the Division of Internal Medicine at the Department of Medical and Surgical Sciences between January 2005 and December 2013 were screened for CD by testing IgA antitransglutaminase (TTG IgA), IgG deamidated gliadin peptides (DGP IgG) and IgA antiendomysium (EMA) antibodies. Of the 230 patients tested, 67 had a diagnosis of rheumatoid arthritis (RA), 52 Sjögren's syndrome (SjS), 42 systemic sclerosis (SCL), 35 systemic lupus erythematosus (SLE), 15 mixed connective tissue disease, 11 polymyositis and 10 dermatomyositis. RESULTS: TTG IgA antibodies were identified in 7/230 cases (3%), 3 in SjS (3/42 - 5.8%), 2 in SCL (2/42 - 4.8%), 1 in RA (1/67 - 1.5%) and 1 in SLE sera (1/35 - 2.8%). All the seven sera were also positive for DGP IgG and EMA IgA. DGP IgG were the most frequent antibody detected, being found in 16 (7%) sera. CONCLUSION: This study identified a high prevalence of CD antibodies in adult patients referred to a rheumatology outpatient clinic. These results highlight the importance of CD screening in subjects presenting with rheumatological features.

Interpretation of serological tests in the diagnosis of celiac disease: Anti-deamidated gliadin peptide antibodies revisited.

Algorithms for celiac disease diagnosis provided by guidelines are based primarily on anti-tissue transglutaminase 2 (TG2) antibodies and/or anti-endomysium antibodies. The place of anti-deamidated gliadin peptide (DGP) antibodies is less well established. This study was designed to assess the clinical relevance of anti-DGP antibodies. Two thousand and twenty-six consecutive unselected patients systematically tested for anti-TG2, endomysium, gliadin, DGP antibodies and IgA dosage were investigated. The serological interpretation was assessed by analyzing the medical records of patients. From the 1984 newly investigated patients suspected of celiac disease, 10% had at least one celiac marker. Anti-TG2, anti-endomysium, anti-gliadin and anti-DGP antibodies were found in 1.1%, 0.6%, 6.8% and 4.1% of cases respectively, with different combinations. The diagnosis of celiac disease was retained in 0.45% of patients. When using the duodenal biopsies as a gold standard, analysis of the anti-DGP diagnosis performance showed that the specificity and the predictive positive value (PPV) were lower than that of the anti-TG2 assay. The combined detection of anti-TG2 and anti-DGP antibodies had a lower PPV than that of anti-TG2 and anti-endomysium antibodies (p = 0.04). When analyzing the contribution of anti-DGP antibodies as an additional marker to both anti-TG2 and anti-endomysium antibodies, the PPV of the three associated antibodies was shown to be significantly lower than the PPV of the both anti-TG2 and anti-endomysium antibodies (p = 0.04). As a conclusion, anti-DGP antibodies may not have the diagnosis value required as an additional screening test to anti-TG2 antibodies for identifying celiac disease patients in medical centers where anti-endomysium detection is available.

Central America in Transition: From Maize to Wheat Challenges and Opportunities.

The Central American countries: Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, and Panama are in transition from a dietary culture based mainly on maize to a wheat-containing diet. Several other changes are occurring, such as a decrease of parasitic and infectious diseases. The environmental changes permit a prediction of an increase of celiac disease and other autoimmune diseases such as type I diabetes and thyroid disease in these genetically heterogeneous countries. At present, celiac disease and gluten-related disorders are considered to be of no relevance at the level of public health in these nations. This review documents the presence of celiac disease in Central America. It draws attention to some of the challenges in planning systematic studies in the region since up until recently celiac disease was unknown. The aim of this review is to disseminate knowledge obtained with preliminary data, to stimulate clinical and basic scientists to study these diseases in Central America and to alert authorities responsible for the planning of education and health, to find possibilities to avoid a rise in these disorders before the epidemics start, as has occurred in the Mediterranean countries.

Adaptive diagnosis of coeliac disease.

Coeliac disease has for a long time simply been regarded as a gluten-dependent enteropathy and a duodenal biopsy was required in all patients for the diagnosis. It is now accepted that autoimmunity against transglutaminase 2 is an earlier, more universal and more specific feature of coeliac disease than histologic lesions. Moreover, high serum levels of combined anti-transglutaminase 2 and anti-endomysium antibody positivity have excellent predictive value for the presence of enteropathy with villous atrophy. This makes the histology evaluation of the gut no longer necessary in well defined symptomatic paediatric patients with compatible HLA-DQ2 and/or DQ8 background. The biopsy-sparing diagnostic route is not yet recommended by gastroenterologists for adults, and certain clinical circumstances (immunodeficiency conditions, extraintestinal manifestations, type-1 diabetes mellitus, age less than 2 years) may require modified diagnostic approaches. Coeliac patients with preserved duodenal villous structure do exist and these need a more extended evaluation by immunologic and molecular biology tools.

Tissue transglutaminase levels above 100 U/mL and celiac disease: a prospective study.

AIM: To investigate whether a tissue-transglutaminase antibody (tTGA) level ≥ 100 U/mL is sufficient for the diagnosis of celiac disease (CD). METHODS: Children suspected of having CD were prospectively included in our study between March 2009 and September 2011. All patients with immune globulin A deficiency and all patients on a gluten-free diet were excluded from the study. Anti-endomysium antibodies (EMA) were detected by means of immunofluorescence using sections of distal monkey esophagus (EUROIMMUN, Luebeck, Germany). Serum anti-tTGA were measured by means of enzyme-linked immunosorbent assay using human recombinant tissue transglutaminase (ELiA Celikey IgA kit Phadia AB, Uppsala, Sweden). The histological slides were graded by a single experienced pathologist using the Marsh classification as modified by Oberhuber. Marsh II and III lesions were considered to be diagnostic for the disease. The positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of EMA and tTGA along with their 95% CI (for the cut off values > 10 and ≥ 100 U/mL) were calculated using histology as the gold standard for CD. RESULTS: A total of 183 children were included in the study. A total of 70 (38.3%) were male, while 113 (61.7%) were female. The age range was between 1.0 and 17.6 years, and the mean age was 6.2 years. One hundred twenty (65.6%) patients had a small intestinal biopsy diagnostic for the disease; 3 patients had a Marsh II lesion, and 117 patients had a Marsh III lesion. Of the patients without CD, only 4 patients had a Marsh I lesion. Of the 183 patients, 136 patients were positive for EMA, of whom 20 did not have CD, yielding a PPV for EMA of 85% (95% CI: 78%-90%) and a corresponding specificity of 68% (95% CI: 55%-79%). The NPV and specificity for EMA were 91% (95% CI: 79%-97%) and 97% (95% CI: 91%-99%), respectively. Increased levels of tTGA were found in 130 patients, although only 116 patients truly had histological evidence of the disease. The PPV for tTGA was 89% (95% CI: 82%-94%), and the corresponding specificity was 78% (95% CI: 65%-87%). The NPV and sensitivity were 92% (95% CI: 81%-98%) and 97% (95% CI: 91%-99%), respectively. A tTGA level ≥ 100 U/mL was found in 87 (47.5%) patients, all of whom were also positive for EMA. In all these 87 patients, epithelial lesions confirming CD were found, giving a PPV of 100% (95%CI: 95%-100%). The corresponding specificity for this cut-off value was also 100% (95% CI: 93%-100%). Within this group, a total of 83 patients had symptoms, at least gastrointestinal and/or growth retardation. Three patients were asymptomatic but were screened because they belonged to a group at risk for CD (diabetes mellitus type 1 or positive family history). The fourth patient who lacked CD-symptoms was detected by coincidence during an endoscopy performed for gastro-intestinal bleeding. CONCLUSION: This study confirms based on prospective data that a small intestinal biopsy is not necessary for the diagnosis of CD in symptomatic patients with tTGA ≥ 100 U/mL.