A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen.

Autoantigen discovery is a critical challenge for the understanding and diagnosis of autoimmune diseases. While autoantibody markers in current clinical use have been identified through studies focused on individual disorders, we postulated that a reverse approach starting with a putative autoantigen to explore multiple disorders might hold promise. We here targeted the epidermal protein transglutaminase 1 (TGM1) as a member of a protein family prone to autoimmune attack.

Simultaneous detection of IgA and IgG antibodies against tissue transglutaminase: The preferred pre-biopsy test in childhood celiac disease.

Objectives: IgA antibodies against tissue transglutaminase (anti-TG2) is a reliable marker of celiac disease (CD). However, IgA-deficient patients are not identified and young children may lack IgA anti-TG2. Combined detection of IgA and IgG (IgA/IgG) against deamidated gliadin peptides (DGP) has shown a high diagnostic performance for untreated CD.

Silent coeliac disease is over-represented in children with type 1 diabetes and their siblings.

Aim: This study measured autoantibodies against tissue transglutaminase (anti-tTG) to detect untreated coeliac disease in children with type 1 diabetes and their siblings.

Methods: Anti-tTG was measured in prospectively collected sera from 169 children at the onset of diabetes, 88 of their siblings and 96 matched control children. Coeliac disease was confirmed with a small intestinal biopsy.

Prevalence and sensitization of atopic allergy and coeliac disease in the Northern Sweden Population Health Study.

Background: Atopic allergy is effected by a number of environmental exposures, such as dry air and time spent outdoors, but there are few estimates of the prevalence in populations from sub-arctic areas.

Objective: To determine the prevalence and severity of symptoms of food, inhalation and skin-related allergens and coeliac disease (CD) in the sub-arctic region of Sweden. To study the correlation between self-reported allergy and allergy test results.

A single conformational transglutaminase 2 epitope contributed by three domains is critical for celiac antibody binding and effects.

The multifunctional, protein cross-linking transglutaminase 2 (TG2) is the main autoantigen in celiac disease, an autoimmune disorder with defined etiology. Glutamine-rich gliadin peptides from ingested cereals, after their deamidation by TG2, induce T-lymphocyte activation accompanied by autoantibody production against TG2 in 1-2% of the population. The pathogenic role and exact binding properties of these antibodies to TG2 are still unclear.

No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls.

Unlabelled: BACKGROUND; Previous studies have indicated that peripheral circulating markers of inflammation are elevated in women with polycystic ovary syndrome (PCOS), but thus far no studies concerning markers of inflammation in adipose tissue have been published. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue.

Methods: Twenty overweight patients with PCOS, 10 lean patients with PCOS and 20 overweight controls had subcutaneous fat biopsies and blood samples taken.

Patients with polycystic ovary syndrome have lower levels of IgM anti-phosphorylcholine antibodies than healthy women.

Introduction: IgM antibodies against phosphorylcholine (IgM anti-PC) are natural autoantibodies, possibly exerting one of the atheroprotective functions of the immune system. Increased levels of these antibodies reduce the development of atherosclerosis in mice, and low levels of IgM anti-PC have been associated with increased risk for cardiovascular disease (CVD). This study compared levels of IgM anti-PC in women with polycystic ovary syndrome (PCOS, n = 111) and healthy controls (n = 79).

Prediction of clinical and mucosal severity of coeliac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase.

Objectives: We analysed whether the quantification of autoantibodies against tissue transglutaminase could be used to predict mucosal destruction and disease severity in patients with gluten sensitivity.

Patients And Methods: One hundred seventy patients with coeliac disease (CD), comprising 52 children with severe malabsorption (group I), 59 children with mild symptoms (group II), 59 adults (group III), 134 patients with dermatitis herpetiformis (DH), and 131 disease controls, were studied. Serial serum samples of patients in groups I and II on a gluten-free diet were also included.

Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: effects on uptake of oxidized LDL in macrophages as a potential mechanism.

Objective: We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in prediction of cardiovascular disease (CVD) and on macrophage uptake of Oxidized LDL (OxLDL).

Methods: From a screening of 4232 subjects, 60-year-old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ischemic stroke, or hospitalized angina pectoris) and 633 age- and sex-matched controls were identified through a 5-7 year follow-up. Serum levels of IgM anti-PC was determined by ELISA.

Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age.

Objectives: The aim was to investigate age-dependent serum levels and occurrence of elevated celiac disease (CD)-related antibodies in young children, to define the optimal serological procedure when selecting for small intestinal biopsy.

Patients And Methods: Included were 428 children with biopsy verified CD (median age 16 months; range 7.5 months-14 years) and 216 controls (median age 2.

Low levels of IgM antibodies against phosphorylcholine-A potential risk marker for ischemic stroke in men.

Background: Natural antibodies specific for phosphorylcholine (anti-PC) have been implicated as protective factors in atherosclerosis. We herein determined the relationship between IgM anti-PC and incidence of cardiovascular disease (CVD).

Methods: We studied 349 incident cases (200 men) of first events of CVD (coronary heart disease (CHD; n=203 or ischemic stroke; n=146) and 693 age- and sex-matched controls identified through 12 years of follow-up (1991-2003) of subjects from the cardiovascular cohort within the Malmö Diet and Cancer Study.

Protein A and protein G ELISA for the detection of IgG autoantibodies against tissue transglutaminase in childhood celiac disease.

Objectives: To investigate if the detection of celiac disease (CD) in children was improved by using alternative conjugates for assessment of tissue transglutaminase (tTG) autoantibodies.

Methods: Serum samples from 108 biopsy confirmed CD children and 42 control subjects were investigated for the presence of autoantibodies with tTG coated microplates using protein A (PA), protein G (PG), anti-IgG, or anti-IgA as conjugates.

Results: Of the 108 CD children, 86 (80%) were IgG-tTG positive, 91 (84%) were positive with the PA-conjugate, 94 (87%) were positive with the PG-conjugate, and 103 (95%) were IgA-tTG positive.

Deamidated gliadin peptides form epitopes that transglutaminase antibodies recognize.

Objective: Deamidated gliadin peptides are efficient antigens in diagnostic tests for celiac disease, and results correlate better with transglutaminase 2-based assays than those with native gliadin. We investigated whether deamidated gliadin antigens are structurally similar to transglutaminase 2 or could mimic transglutaminase epitopes.

Patients And Methods: Serum samples from 74 celiac and 65 control patients, and 13 different transglutaminase 2-specific monoclonal mouse antibodies were investigated for their binding to commercially available deamidated gliadin peptides using enzyme-linked immunosorbent assay, competition studies, and molecular modelling.

Autoantibodies against soluble and immobilized human recombinant tissue transglutaminase in children with celiac disease.

Objectives: The conformation of tissue transglutaminase might influence the performance of immunoassays to detect autoantibodies from patients with celiac disease. The present study investigated how the exposure of tissue transglutaminase kept in a liquid phase and fixed to a solid support affected the binding of immunoglobulin (Ig)A and IgG autoantibodies in children with untreated and treated celiac disease.

Methods: Included were 73 untreated celiac disease children, 50 controls and 80 children with treated celiac disease.

Antitissue transglutaminase and antithyroid autoantibodies in children with Down syndrome and celiac disease.

Objectives: We measured circulating autoantibodies and evaluated the potential of circulating antitissue transglutaminase (tTG) antibodies to determine the presence of celiac disease (CD) in children with Down syndrome.

Methods: An ELISA based on recombinant human tTG was used to measure the levels of immunoglobulin A and immunoglobulin G antibodies in serum samples from 72 children with Down syndrome, 52 children with biopsy-verified CD, 21 disease controls with a normal small intestinal mucosa and 23 healthy controls. Of the 72 Down syndrome children, 11 under-went a small intestinal biopsy.

Immunoglobulin G (IgG) anti-tissue transglutaminase antibodies used as markers for IgA-deficient celiac disease patients.

The role of immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (IgA-tTG) as predictors of untreated celiac disease (CoD) is well documented, and the presence and levels of these antibodies are most accurately monitored with native or recombinant human antigens. However, IgA-deficient CoD patients are not identified by IgA serology, and conflicting results concerning the diagnostic validity of IgG antibodies against gliadin (IgG-AGA), endomysium (IgG-EmA), and tTG (IgG-tTG) have been reported. The aim of the present study was to evaluate the utility of IgG-tTG for the detection of CoD in IgA-deficient patients.

Prevalence of Celiac disease among children in Finland.

Background: Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the disease and tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease and that positive findings correlate with specific HLA haplotypes.

Methods: Serum samples were collected from 3654 students (age range, 7 to 16 years) in 1994 and screened in 2001 for endomysial and tissue transglutaminase antibodies.

Recombinant human tissue transglutaminase for diagnosis and follow-up of childhood coeliac disease.

Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions and for rapid follow-up. The aim of this study was to evaluate the potential of circulating anti-tissue transglutaminase (tTG) IgA and IgG antibodies in the diagnosis and follow-up of childhood celiac disease. An ELISA using recombinant human tTG was used to measure the levels of IgA and IgG anti-tTG antibodies in 226 serum samples from 57 children with biopsy-verified celiac disease, 29 disease control subjects, and 24 healthy control subjects.