Most cited article - PubMed ID 9400629
Anti-gliadin antibodies in patients with celiac disease cross-react with enterocytes and human calreticulin
Latent autoimmune diabetes of adults (LADA) manifested after the age of 35 is characterized by the presence of disease-specific autoantibodies (anti-glutamate decarboxylase GADAb, anti-IA2Ab). However, autoimmunity in Type 1 diabetes mellitus is not targeted only to pancreatic beta-cells. No data have so far been published concerning the antibodies associated with other autoimmune disease in LADA patients. The presence of anti-thyroglobulin (TGAb), anti-thyroid peroxidase (TPOAb), anti-gliadin IgA (AGAAb) and IgG (AGGAb) and endomysial antibodies (EMAb) in sera of 68 diabetics typed as LADA was compared with the antibody presence in sera of 85 patients with Type 2 diabetes. We found a significantly higher occurrence of gliadin antibodies in LADA patients: the rate of AGGAb was 19.1% in comparison with 3.5% in the T2DM group (P = 0.0026), the rate of AGAAb was 13.2% in comparison with 3.5% (P = 0.035). The prevalence of EMAb was very low in both groups (1.5% and 0). The two groups differed significantly in the TPOAb rate: 22.1% in LADA compared to 9.4% in T2DM (P = 0.04), whereas no significant difference was found in the presence of TGAb (8.8% and 3.5%, P = 0.187). In comparison with T2DM patients, LADA patients were found to express higher antibody activity against gluten-related antigens and against TPO.
- MeSH
- Autoantibodies analysis MeSH
- Diabetes Mellitus, Type 1 immunology MeSH
- Diabetes Mellitus, Type 2 immunology MeSH
- Diabetes Mellitus immunology MeSH
- Gliadin immunology MeSH
- Immunoglobulin A immunology MeSH
- Immunoglobulin G immunology MeSH
- Iodide Peroxidase immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Antibodies, Anti-Idiotypic analysis MeSH
- Chi-Square Distribution MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Thyroglobulin immunology MeSH
- Age of Onset MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Autoantibodies MeSH
- Gliadin MeSH
- Immunoglobulin A MeSH
- Immunoglobulin G MeSH
- Iodide Peroxidase MeSH
- Antibodies, Anti-Idiotypic MeSH
- Thyroglobulin MeSH
The prevalence of celiac disease (CD) was determined in healthy blood donors and in high-risk groups of adults (a total of 1835 adults--randomly selected 1312 healthy blood donors, 102 patients with primary osteoporosis, 58 patients with autoimmune diseases and 365 infertile women). It was calculated on the basis of a two-step serologic screening method--in the first step IgA and IgG antigliadin antibodies (AGA) and IgA anti-gamma-glutamyltransferase ('transglutaminase') antibodies (ATG) were estimated, in the second step sera positive for IgA AGA and/or IgA ATG were examined for antiendomysial IgA (AEA) antibodies. Immunoenzymic assay (ELISA) was used for determining of AGA and ATG antibodies; immunofluorescence method, performed on human umbilical cord tissue, was used for assaying of AEA antibodies. Total serum IgA level in only IgG AGA positive subjects was measured by routine turbidimetric method. 0.45% of healthy blood donors, 0.98% of osteoporotic patients, 2.7% of patients suffering from autoimmune disease and 1.13% of women with infertility considered as immunologically mediated were found to be positive in both steps of serologic screening (AGA and/or ATG and antiendomysium positive). The presumed high prevalence of seropositivity for CD in apparently healthy Czech adult population was confirmed. In the high-risk groups, the prevalence of seropositivity for CD was approximately 2-4 times higher than in healthy blood donors. The real prevalence of CD in the tested groups, however, can be estimated after performing small intestinal biopsy in the seropositive patients.
- MeSH
- Autoimmune Diseases complications MeSH
- Celiac Disease complications diagnosis epidemiology immunology MeSH
- Adult MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- gamma-Glutamyltransferase immunology MeSH
- Gliadin immunology MeSH
- Immunoglobulin A blood MeSH
- Immunoglobulin G blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Osteoporosis complications MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Seroepidemiologic Studies MeSH
- Infertility, Female complications MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- gamma-Glutamyltransferase MeSH
- Gliadin MeSH
- Immunoglobulin A MeSH
- Immunoglobulin G MeSH
Adhesive interactions between endothelium and circulating cells are crucial for the development of inflammatory reactions. We found significantly higher serum levels of soluble intracellular adhesion molecule-1 (sICAM-1, 492.5 +/- 22.1 ng/ml) in patients with active celiac disease (including IgA-deficient patients) than in patients on a gluten-free diet (335.7 +/- 20.0 ng/ml) (P < 0.001) and healthy controls (207.4 +/- 11.2 ng/ml) (P < 0.001). The concentration of soluble E-selectin in sera from celiac patients (37.2 +/- 3.4 ng/ml) was also higher (P < 0.001) than in sera from healthy controls (15.5 +/- 0.7 ng/ml) but, in contrast to sICAM-1, it remained high in the patients after treatment (30.2 +/- 2.7 ng/ml). Interestingly, the concentration of circulating soluble interleukin-2 receptors, molecules indicating lymphocyte activation, was only increased in sera from patients with active celiac disease (2943.0 +/- 214.1 pg/ml), and the level in sera from treated patients and healthy controls was comparable (1936 +/- 349 and 1416 +/- 111.7 pg/ml). The elevated serum level of soluble cell adhesion molecules could be used as a supplementary, noninvasive procedure for monitoring intestinal immune reactions.
- MeSH
- Celiac Disease blood diet therapy MeSH
- Child MeSH
- Adult MeSH
- E-Selectin blood MeSH
- Infant MeSH
- Humans MeSH
- Intercellular Adhesion Molecule-1 blood MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Receptors, Interleukin-2 blood MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- E-Selectin MeSH
- Intercellular Adhesion Molecule-1 MeSH
- Receptors, Interleukin-2 MeSH
BACKGROUND: Sera of patients with coeliac disease, containing IgA and IgG antigliadin antibodies (AGA) and various IgA autoantibodies, react with isolated enterocytes. AGA cross react with enterocyte antigens, one of which has been identified as calreticulin. AIMS: To characterise the antigenic structures of gliadin, enterocytes, and calreticulin recognised by AGA from patients with active coeliac disease. METHODS: AGA were isolated from sera of nine patients by affinity chromatography and tested by competitive ELISA using 40 alpha-gliadin synthetic dodecapeptides (A1-F6). RESULTS: Reactivity of gliadin with all purified AGA tested was inhibited by peptide A4 at the N-terminal region; by C2, C3, and D4 at the central region; and by F3 and F4 at the C-terminal region of the gliadin molecule. AGA cross reactivity with enterocytes was inhibited by peptides A4, D1-D4, and F6 and with calreticulin by peptides A4, D3, and D4. As dominant epitopes AGA of coeliac patients recognise similar structures corresponding to peptides A4, D3, D4, and F6 present on gliadin, enterocytes, and calreticulin. Substitution of glutamine in the A4 peptide by glutamic acid caused loss of inhibitory capacity. Shortening of peptide A4 on the N-terminal by three amino acids increased its inhibitory effect. CONCLUSIONS: AGA of patients with coeliac disease react with similar structures on gliadin and potential autoantigens on enterocytes.
- MeSH
- Autoantigens immunology MeSH
- Autoimmune Diseases immunology MeSH
- Celiac Disease immunology MeSH
- Chromatography, Affinity MeSH
- Adult MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Epitopes analysis MeSH
- Gliadin chemistry immunology MeSH
- Calreticulin MeSH
- Rats MeSH
- Humans MeSH
- Peptide Fragments immunology MeSH
- Rats, Wistar MeSH
- Calcium-Binding Proteins immunology MeSH
- Antibodies blood MeSH
- Ribonucleoproteins immunology MeSH
- Intestines immunology MeSH
- Cross Reactions MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Rats MeSH
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Autoantigens MeSH
- Epitopes MeSH
- Gliadin MeSH
- Calreticulin MeSH
- Peptide Fragments MeSH
- Calcium-Binding Proteins MeSH
- Antibodies MeSH
- Ribonucleoproteins MeSH