ABSTRACT
Children with type 1 diabetes (T1D) are at increased risk of celiac disease (CD). The replacement of insulin in T1D, and the exclusion of gluten in CD, are lifelong, burdensome treatments. Compliance to a gluten-free diet (GFD) in children with CD is reported to be high, while compliance in children with both diseases has scarcely been studied. To examine compliance to a GFD in children with both T1D and CD, we analyzed tissue transglutaminase IgA-antibodies (tTGA). Moreover, associations between compliance and age, sex, glycemic control, ketoacidosis (DKA), body mass index (BMI), and time of CD diagnosis were investigated. Of the 743 children diagnosed with T1D in southern Sweden between 2005 and 2012, 9% were also diagnosed with CD. Of these, 68% showed good compliance to a GFD, 18% showed intermediate compliance, and 14% were classified as non-compliant. Higher age, poorer HbA1c, and more DKAs were significantly (p < 0.05) associated with poorer compliance. In conclusion, we found that compliance to a GFD in children with T1D and CD is likely be lower than in children with CD only. Our results indicate that children with both T1D and CD could need intensified dietary support and that older children and children with poor metabolic control are especially vulnerable subgroups.
Subject(s)
Celiac Disease/diet therapy , Diabetes Mellitus, Type 1/diet therapy , Diet, Gluten-Free/methods , Patient Compliance , Adolescent , Age Factors , Body Mass Index , Celiac Disease/epidemiology , Child , Child, Preschool , Diabetes Mellitus, Type 1/epidemiology , Diabetic Ketoacidosis/epidemiology , Female , Glycated Hemoglobin/analysis , Humans , Immunoglobulin A/immunology , Infant , Male , Protein Glutamine gamma Glutamyltransferase 2/immunology , Sex Factors , Sociodemographic Factors , SwedenABSTRACT
Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. In patients with suspected celiac disease, measurement of serum IgA antibodies to tissue transglutaminase-2 has a high sensitivity and specificity and is the first screening test that should be ordered. The diagnosis of celiac disease is based on the presence of mucosal damage in small intestinal biopsies in patients having circulating celiac disease-specific antibodies. Celiac disease management includes lifelong adherence to a gluten-free diet and continuous long-term follow-up.
Subject(s)
Celiac Disease/diet therapy , Celiac Disease/diagnosis , Adolescent , Biopsy/methods , Celiac Disease/epidemiology , Celiac Disease/immunology , Child , Child, Preschool , Diet, Gluten-Free/methods , Female , Glutens/immunology , Humans , Immunoglobulin A/blood , Infant , Intestinal Mucosa/pathology , Intestines/pathology , Male , Protein Glutamine gamma Glutamyltransferase 2/immunologyABSTRACT
A hallmark of celiac disease is the gluten-dependent production of antibodies specific for deamidated gluten peptides (DGP) and the enzyme transglutaminase 2 (TG2). Both types of antibodies are believed to result from B cells receiving help from gluten-specific CD4+ T cells and differentiating into antibody-producing plasma cells. We have here studied the collaboration between DGP- and TG2-specific B cells with gluten-specific CD4+ T cells using transgenic mice expressing celiac patient-derived T-cell and B-cell receptors, as well as between B-cell transfectants and patient-derived gluten-specific T-cell clones. We show that multivalent TG2-gluten complexes are efficient antigens for both TG2-specific and DGP-specific B cells and allow both types of B cells to receive help from gluten-specific T cells of many different specificities.
Subject(s)
Celiac Disease/genetics , Glutens/genetics , Protein Glutamine gamma Glutamyltransferase 2/genetics , Receptors, Antigen, B-Cell/genetics , Animals , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Celiac Disease/immunology , Celiac Disease/pathology , Gliadin/genetics , Gliadin/immunology , Glutens/immunology , Humans , Mice , Mice, Transgenic , Protein Glutamine gamma Glutamyltransferase 2/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathologyABSTRACT
BACKGROUND: Test utilization for the diagnosis of celiac disease may affect the prevalence and incidence of the disease in Korea. We aimed to investigate the test utilization of serological biomarkers for celiac disease in Korea. METHODS: We retrospectively investigated the test utilization of tissue transglutaminase IgA, gliadin IgA and IgG, and endomysial IgA antibody (Ab) assays between January 2011 and June 2020. RESULTS: During a nine-year-and-six-month study period, overall 307,322,606 clinical tests were requested from different clinical settings, such as local clinics, hospitals, university hospitals, and tertiary medical centers. Among them, only 58 tissue transglutaminase IgA, 22 gliadin IgA, 12 gliadin IgG, and 16 endomysial IgA Ab tests were performed on 79 Korean patients. Among them, one patient had positive transglutaminase IgA Ab result (1.3%). CONCLUSION: Low prevalence and incidence of celiac disease in Korea may be due to an underutilization of diagnostic assays.
Subject(s)
Celiac Disease/diagnosis , Serologic Tests/statistics & numerical data , Celiac Disease/epidemiology , Diagnostic Tests, Routine , Gliadin/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Protein Glutamine gamma Glutamyltransferase 2/immunology , Republic of Korea/epidemiology , Retrospective StudiesABSTRACT
Coeliac disease (CD) is an autoimmune gastroenteropathy triggered by gliadin and gliadin-tissue transglutaminase (tTG) complexes. CD is one of the few autoimmune diseases with an accurate, non-invasive serological test. Anti-endomysial, anti-tTG and anti-deaminated gliadin peptides (DGP) antibodies are currently used for serological tests with tTG ELISAs being the superior test. Duodenal biopsy, although invasive, is the gold standard for CD diagnosis. HLA genotyping and flow cytometry can also be used as supplementary tests. The incidence of CD is rising globally although the reasons for this remain unclear. In addition, the true incidence of coeliac disease in African populations remains unknown although recent work suggests that South African populations express the alleles associated with this disease. This review examines the pathogenesis and diagnosis of coeliac disease and considers novel and innovative biomarkers in its diagnosis specifically in an African population.
Subject(s)
Antibodies/immunology , Celiac Disease/diagnosis , Duodenum/immunology , Gliadin/immunology , HLA Antigens/immunology , Protein Glutamine gamma Glutamyltransferase 2/immunology , Biomarkers , Celiac Disease/genetics , Celiac Disease/immunology , HLA Antigens/genetics , HumansABSTRACT
Celiac disease (CeD) is a T-cell-dependent enteropathy with autoimmune features where tissue transglutaminase (TG2)-mediated posttranslational modification of gliadin peptides has a decisive role in the pathomechanism. The humoral immune response is reported to target mainly TG2-deamidated γ-gliadin peptides. However, α-gliadin peptides, like p57-68, playing a crucial role in the T-cell response, and p31-43, a major trigger of innate responses, also contain B-cell gliadin epitopes and γ-gliadin like motifs. We aimed to identify if there are anti-gliadin-specific antibodies in CeD patients targeting the p31-43 and p57-68 peptides and to examine whether deamidation of these peptides could increase their antigenicity. We explored TG2-mediated deamidation of the p31-43 and p57-68 peptides, and investigated serum antibody reactivity toward the native and deamidated α and γ-gliadin peptides in children with confirmed CeD and in prospectively followed infants at increased risk for developing CeD. We affinity-purified antibody populations utilizing different single peptide gliadin antigens and tested their binding preferences for cross-reactivity in real-time interaction assays based on bio-layer interferometry. Our results demonstrate that there is serum reactivity toward p31-43 and p57-68 peptides, which is due to cross-reactive γ-gliadin specific antibodies. These γ-gliadin specific antibodies represent the first appearing antibody population in infancy and they dominate the serum reactivity of CeD patients even later on and without preference for deamidation. However, for the homologous epitope sequences in α-gliadins shorter than the core QPEQPFP heptapeptide, deamidation facilitates antibody recognition. These findings reveal the presence of cross-reactive antibodies in CeD patients recognizing the disease-relevant α-gliadins.
Subject(s)
Autoantibodies/immunology , Celiac Disease/metabolism , Gliadin/metabolism , Peptide Fragments/metabolism , Protein Glutamine gamma Glutamyltransferase 2/immunology , Adolescent , Amides/chemistry , Autoantibodies/metabolism , Celiac Disease/immunology , Child , Child, Preschool , Cross Reactions , Epitopes/immunology , Gliadin/immunology , Humans , Infant , Peptide Fragments/immunology , Protein Glutamine gamma Glutamyltransferase 2/chemistry , Protein Glutamine gamma Glutamyltransferase 2/metabolismSubject(s)
B-Lymphocytes/immunology , Celiac Disease/immunology , Intestinal Mucosa/immunology , Intestines/immunology , Intestines/pathology , Animals , Atrophy , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Disease Models, Animal , Glutens/adverse effects , HLA-DQ Antigens/immunology , Interferon-gamma/immunology , Mice , Protein Glutamine gamma Glutamyltransferase 2/immunologyABSTRACT
Immune checkpoint inhibitors (ICI) reinvigorate the immune system to recognize and destroy tumor cells. Because of this biological mechanism, patients might develop autoimmune toxicities, notably in the digestive tract (most frequently, hepatitis or colitis). A 70-year-old man with relapsed mesothelioma was treated with nivolumab in 3rd line. He was hospitalized for watery and foul-smelling diarrhea. He underwent gastrointestinal endoscopy, showing duodenitis and villous atrophy and measurement of serum IgA antibodies to tissue transglutaminase (tTG-IgA+), leading to the diagnosis of ICI-induced celiac disease. He was treated with steroids, proton pump inhibitors, and a gluten-free diet. If ICI-induced celiac disease is rare in the literature, increasing reports suggest that celiac disease might represent an underestimated ICI toxicity. This case highlights the necessity of complementary investigation (including tTG-IgA and endoscopic biopsies) in patients with atypical digestive symptoms during immunotherapy.