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Genetic background of coeliac disease has been subjects to intensive research since decades. However, only results of HLA phenotyping have been taken over to routine clinical practice. Meanwhile, data on the role of epigenetical factors in the manifestation of diseases have been emerging. In coeliac disease, there are several questions both in the fields of genetics and epigenetics yet to be answered. In this review, a cross section of current knowledge on these issues is presented with special interest regarding the future clinical applications.

Celiac disease or gluten-sensitive enteropathy is the most common disease of jejunum, leading to malabsorption. It is an immune mediated disease induced by gluten at the presence of genetic predisposition. After gluten exposition, immune processes are induced by T-cell mediation causing typical intestinal and extra intestinal manifestations. The diagnosis of celiac disease is still set up on the result of jejunal biopsy and detecting of antibodies against endomysium and tissue transglutaminase. From genetic aspect, association with HLA DQ2/DQ8 is identified in celiac disease. On a strict gluten-free diet, the clinical, histological and serological results improve and remission of accompanying diseases may be achieved. In the etiopathogenesis of celiac disease several genetic and immunological mechanisms have been recognized in recent years. Connected to the accompanying diseases, more reviews have been issued about the bone metabolic changes and less about the inflammatory join disorders. In the present work, the authors review literature data that reveal common background from both immunological and genetic aspects.

Clinical presentations of the celiac disease and inflammatory bowel diseases (IBD) are highly variable, but little is known about those factors determining disease phenotype. Since differences in the antioxidant, scavenging and immunomodulatory properties were found among 3 major haptoglobin (Hp) phenotypes. The aim of our study was to investigate the distribution of Hp polymorphisms in large cohort celiac patients and in patients with IBD, and also their possible association with the clinical presentation of these diseases. Hp phenotypes were determined by sodium-dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting of the sera, which clearly identifies the genotypes. In celiac patients, the frequency of Hp 2-1 phenotypes was significantly higher compared to the control population. The occurrence of Hp 2-2 was lower; however, patients having this phenotype were at an increased risk of severe malabsorption as a clinical presentation of the disease but reduced risk of silent disease. In Crohn's disease (CD), patients with Hp 2-1 type carried a higher probability for inflammatory form compared to the other two phenotypes, while the stricturing form developed less frequently. In patients with primary sclerosing cholangitis we found no Hp 1-1 expression. The role of Hp molecules may be explained by their distinct immunomodulatory properties and structural characteristics. Sero-reactivity to microbial components or perinuclear components of neutrophils (atypical P-ANCA) is reported to be associated with disease phenotype and may be of diagnostic importance in IBD. The aim of our study was to investigate the prevalence of serological markers in a large cohort of IBD patients. We also assessed the possible interaction with the disease phenotype and studied the relationship between serological response and genetic factors. Sera were assayed for Saccharomyces cerevisiae (ASCA) and outer membrane porin protein of Escherichia coli (anti-Omp) by enzyme-linked immunosorbent assay (ELISA) and ANCA by indirect immunofluorescence method. Serological markers proved to be useful in differential diagnosis of IBD. In a logistic regression analysis, ASCA and anti-Omp were independently associated with ileal and non-inflammatory disease, but not with a risk for surgery. The number of antibodies produced against microbial antigen and their titers in CD showed a positive correlation with the small bowel involvement and the severity of the disease course (serology dosage effect). Reactivity to microbial components was associated with caspase recruitment domain (NOD2/CARD15) genotype. Positive correlation was found between the number of mutations and the prevalence of antimicrobial antibodies (gene dosage effect), further supporting the role of altered microbial sensing in the pathogenesis of CD.

Introduction: Coeliac disease (gluten sensitive enteropathy) is a very frequent disease appearing in variegated clinical form. In the last decade--concerning the immunogenetic and immunopathological aspects of the disease many of new recognition came to alight., Aim: As the disease can lay hidden in its non classical manifesting form for a very long time, authors wished to study the efficacy of screening, which may be introduced for patients attending immunological outpatient care service., Patients, Methods and Results: In the frame of nation-wide patient care, out of the 200 potential patients sent for immunological check up, various form of coeliac disease was diagnosed in 20 cases. Among these cases there are two--presented for the first time--which are connected to bone marrow transplantation. Based on the immunogenetics and autoantibody serology as well as on small intestine biopsies the following conclusions were made., Conclusion: 1. Coeliac disease in Hungary is very frequent. Hidden disease should be considered first of all in cases of malabsorption symptoms. 2. Demonstration of autoantibodies on wide-scale palette helps to state the diagnosis based on the systematic auto-immune disease connection. 3. Study of Human Leukocyte Antigen allotype (HLA-DQA1*0501/DQBI*02) applied as marker can considerably support the suspicion of disease. 4. Histology test of the small intestine cannot be omitted.

Coeliac disease is the most common disorder with malabsorption of the small intestine, caused by the gluten fraction of cereals in genetically predisposed individuals. T-cell mediated autoimmune processes are initiated by gluten exposure, leading to both intestinal and extraintestinal manifestations, therefore coeliac disease is nowadays considered to be a systemic disorder. More and more diseases are proved to be associated with coeliac disease, in these conditions screening is strongly recommended. The studying of the recently explored autoantibodies against tissue transglutaminase brought us further in the understanding of the pathophysiology of coeliac disease. The spreading of reliable serologic methods modified our knowledge on the clinical picture and prevalence of the disease. In case of long-term dietary abuse the most common complications are decreased bone mineral density and development of lymphomas. Sustained glutenfree diet results in clinical and histological restitution, affects the course of associating diseases beneficially and decreases the risk for malignancies.

Among 228 relatives of 101 gluten-sensitive patients, 13 anti-endomysium antibody (EmA) positive persons (7 children and 6 adults) were identified. In 12/13 cases jejunal biopsy confirmed severe villous atrophy consistent with celiac disease. In the single EmA positive sibling without villous atrophy the histology is thought to be influenced by a steroid treatment because of pulmonary disease. By routine EmA-testing 12 unexpected EmA positive patients were found out of 756 children with complaints and laboratory results otherwise not justifying jejunal biopsy at the first evaluation. Their initial diagnoses were: proteinuria, colitis, Crohn's disease, rickets, recurrent vomiting, resolved postinfectious lactase deficiency, "previously excluded" celiac disease. Severe villous atrophy could be demonstrated in all EmA positive patients subsequently. In further 204 EmA negative children the biopsy showed no atrophy. EmA positivity may reveal clinically not apparent severe villous atrophy emphasizing the role of a new non invasive and highly specific serological screening method for celiac disease.