Aeskukipp Institute

Wendelsheim, Germany

Aeskukipp Institute

Wendelsheim, Germany
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Lerner A.,Aeskukipp Institute | Lerner A.,Technion - Israel Institute of Technology | Matthias T.,Aeskukipp Institute
International Journal of Celiac Disease | Year: 2015

Celiac disease, once deemed to be primarily a pediatric disease, is accepted nowadays as a lifelong disease that increasingly affects the elderly. In older patients it is late and underdiagnosed, it is hypo- or asymptomatic and case finding strategy is recommended. Gluten restrictive therapy is problematic but manageable and beneficial, improving symptoms, serology, histology and preventing complications. Increased knowledge and awareness on CD in the third age and a comprehensive, multidisciplinary and holistic approach will improve their outcome. © Science and Education Publishing.


Lerner A.,Technion - Israel Institute of Technology | Jeremias P.,Aeskukipp Institute | Matthias T.,Aeskukipp Institute
International Journal of Celiac Disease | Year: 2015

Epidemiological data provide evidence of a steady rise in autoimmune disease throughout Westernized societies over the last decades. Multiple publications exist, describing past or actual incidences/prevalence of individual autoimmune diseases, however, long term studies on selected populations are scarce. Aims: to calculate the % increases per year of autoimmune diseases frequencies worldwide, analyze the differential increases per country and disease, and identify geoepidemiological trends. Methods: A systematic review was performed to identify incidence and prevalence of autoimmune diseases. 30 Studies from the last 30 years were identified using Medline, Google, and Cochrane Library databases. Only long-term regional or national follow-ups are reported. Results: The means ± s.d. of the net % increased /year incidence and prevalence of autoimmune diseases worldwide were 19.1±43.1 and 12.5±7.9, respectively. Rheumatic, endocrinological, gastrointestinal and neurological autoimmune diseases revealed the following annual % increases per year: 7.1, 6.3, 6.2, and 3.7, respectively. In all of these, differences between old vs new frequencies were highly significant (p < 0.0001). Comparing various autoimmune diseases, celiac disease increased the most and the highest increase in incidence, comparing old to new surveys is allocated to myasthenia gravis. Despite considerable variations between the countries, celiac, type 1 diabetes and myasthenia gravis frequencies increased the most in Canada, Israel and Denmark, respectively. Frequencies of the autoimmune diseases increased significantly in the West and North when compared to East and South, respectively. Conclusions: Despite multiple reports on autoimmune diseases frequencies, long-term longitudinal follow-ups are scarce. Incidences and prevalences have increased significantly over the last 30 years. Rheumatic, endocrinological and gastrointestinal autoimmune diseases in Israel, Netherlands, USA and Sweden increased the most. These observations point to a stronger influence of environmental factors as opposed to genetic factors on autoimmune disease development. © Science and Education Publishing.


Lerner A.,Aeskukipp Institute | Lerner A.,Technion - Israel Institute of Technology | Jeremias P.,Aeskukipp Institute | Matthias T.,Aeskukipp Institute
International Journal of Celiac Disease | Year: 2015

Detection of IgA-transglutaminase2 (TG2) autoantibodies has become the test of choice for the diagnosis and monitoring of celiac disease (CD), and is recommended as the serological 'gold standard' by most of the CD societies. Despite its wide acceptance and reasonable performance, several aspects are problematic and disputed. The normal range levels between positivity and negativity are modified, manufacturers' cut-off levels are extremely variable, far from matching in house determinations, insufficient standardization, inadequate reference protocols and no reliable quality assessment of the ELISA antibody (AB) kits for CD diagnosis and follow-up of dietary adherence. Numerous limitations exist in its detection, diagnosis, and follow-up capacities, resulting in frequent clinical circumstances when professionals encounter false positive and negative situations. The present review updates and discusses these facets and aims to extend our knowledge and help CD associated professionals to use the IgA-TG2 antibodies appropriately. We hope that the content of the review will stimulate the scientific community to explore and better delineate the role and functions of the AB and the industrial manufacturers to improve clinical performance of their diagnostic tests. © Science and Education Publishing.


Lerner A.,Technion - Israel Institute of Technology | Matthias T.,Aeskukipp Institute
International Journal of Celiac Disease | Year: 2015

The first description of celiac disease associated with dilated cardiomyopathy and pellagra in the same person, brings multiple interesting aspects to discuss. Celiac disease is prevalent in cardiac failure and vice versa, multiple cardiac manifestations exist in celiac disease. Pathophysiologically, autoimmune, nutritional, infectious and thrombophilic pathways can be involved. In some cases the cardiomyopathy respond to gluten free diet. Multiple cutaneous manifestations, including pellagra like rash, were described in CD. Autoimmune mechanisms and much more, (e.g. nutrient deficiencies) might aggravate the skin manifestation. The present editorial highlights the cardiac-cutaneous-intestinal cross talks in celiac disease in order to increase the awareness of the physician community to speed up celiac disease diagnosis in those extraintestinal manifestations. © Science and Education Publishing.


Lerner A.,Technion - Israel Institute of Technology | Neidhofer S.,Aeskukipp Institute | Matthias T.,Aeskukipp Institute
International Journal of Celiac Disease | Year: 2015

The new 2012 ESPGHAN guidelines for the pediatric diagnosis of celiac disease (CD) unraveled and stimulated an old/new discussion on the most efficient case- finding in pediatric CD. The fine balance between reliable serological markers and the gold diagnostic standard of small bowel histology is somewhat better understood. Due to a low diagnostic rate, changes in phenotype, increased incidence, epidemiological shifts, importance of early implementation of gluten free diet to prevent complications, the case-finding of CD should be improved. Our adult gastrointestinal colleagues did not adopt ESPGHAN diagnostic criteria and within the pediatric gastroenterology community, controversies exist. The present editorial on pediatric CD complements an adult CD one. It expands on the drawbacks, limitations and criticisms of the guidelines and calls for prudency, further research and follow-up studies. Until recent observations are implemented in the future guidelines, small bowel histology should remain the gold standard for case-finding in CD. © Science and Education Publishing.


Lerner A.,Aeskukipp Institute | Lerner A.,Technion - Israel Institute of Technology | Matthias T.,Aeskukipp Institute
International Journal of Celiac Disease | Year: 2016

The gold standard for diagnosis of celiac disease is positive serology confirmed by histological evidence of small intestinal biopsy damage as determined by the modified Marsh classification. Intraepithelial lymphocyte count has a pivotal importance in this grading criteria and the normal cut-off density has paramount importance in distinguishing between celiac disease and normal or false+ conditions. However its determination is problematic, complicated and far from being standardized. The localization along the villi or along the small bowel, the section thickness, the mode of detection and analysis, geoepidemiological influences, age dependency, associated infections or diseases and the strictness of the inclusions/exclusion criteria of the normal control group, all affect IEL density and normal cut-off levels. It is hoped that after standardization, the cut-off levels of IELs will better reflect the in-vivo reality to distinguish celiac disease from normal and associated conditions that affect intestinal IEL count. © Science and Education Publishing.


Baerlecken N.T.,Leibniz University of Hanover | Nothdorft S.,Leibniz University of Hanover | Stummvoll G.H.,Medical University of Vienna | Sieper J.,Charité - Medical University of Berlin | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Background Spondyloarthritis (SpA) is a common debilitating inflammatory disorder. Establishing the diagnosis is often difficult, since abnormalities in conventional X-ray develop with a latency of several years and only HLA-B27 is used as a laboratory marker. The goal of our study was to identify new autoantibodies as diagnostic markers of SpA. Methods: Protein array technology was used to screen for new autoantigens in ankylosing spondylitis. Then, the results were confirmed by ELISA using Class II-associated invariant chain peptide domain of CD74 as antigen. Sera for the ELISA were obtained from 216 patients with axial (n=156) and peripheral (n=60) SpA. Sera of patients with psoriatic arthritis without axial involvement as another subtype of peripheral SpA, rheumatoid arthritis, systemic lupus erythematosus, HIV infection and blood donors served as controls. All donors provided informed consent for the study which was approved by the local ethics committee ( project number 4928). Results: Using protein arrays, we detected IgG antibodies against CD74 in SpA sera. Using ELISA technology on sera that had previously been frozen for several years, IgG autoantibodies against CD74 were found in 67% of the SpA patients and were even more frequent in patients with a short disease duration. In the controls, the prevalence of the new autoantibodies was 18/40 (45%) in psoriatic arthritis without axial involvement, 9/80 (11%) in rheumatoid arthritis, 6/40 (15%) in systemic lupus erythematosus, 1/40 (2.5%) in HIV and 1/125 (0.8%) in blood donors. Conclusions: Antibodies against CD74 could provide an important additional tool for diagnosis of SpA.


Ben-Ami Shor D.,Tel Aviv University | Blank M.,Tel Aviv University | Reuter S.,Aeskukipp Institute | Matthias T.,Aeskukipp Institute | And 4 more authors.
Journal of Autoimmunity | Year: 2014

Background: Lupus nephritis is known to be associated with several antibodies including autoantibodies that target the DNA, C1q and histone, α-actinin, and the nucleosome. In addition, circulating anti-phosphoribosomal protein antibodies (anti-Ribos.P) were found to be associated with lupus nephritis. Study objective: We have assessed the direct role of anti-Ribos.P in the development of glomerulonephritis in-vitro and in animal models. Study design: NZBxW/F1 lupus prone mice were immunized with recombinant Ribos.P0 (rRibos.P). Evaluation of renal disease included mice evaluation for proteinuria and histologic analysis of the kidneys. Anti-Ribos.P monoclonal Ab was prepared from the rRibos.P immunized NZBxW/F1 mice by hybridoma technology. MAPKs expression was analyzed by MAPKs protein array and confirmed by real-time PCR and western blot. To elucidate whether anti-Ribos.P induce glomerulonephritis, naïve C3H mice were immunized with recombinant rRibos.P and the glomerulonephritis was followed up as described above. Results: The immunized NZBxW/F1 lupus prone mice developed anti-Ribos.P which was cross reactive with Sm and not dsDNA. The mice developed accelerated glomerulonephritis manifested by early proteinuria and immunoglobulin deposites in the mesangium of the kidneys. Anti-Ribos.P deposited in the glomerular mesangium were eluted from the kidney. The Ribos.P immunized naïve C3H/Hen mice developed glomerulonephritis manifested by circulating autoantibodies directed to Ribos.P, dsDNA and Sm. The anti Ribos.P were cross reactive with Sm but not with dsDNA, and were deposited in the glomeruli. Interestingly these mice developed alopecia. In vitro. Primary mesangial cells exposed to mouse anti-Ribos.P mAb originated from the immunized lupus mice and to human anti-Ribos.P Abs, induced activation of mesangial cells via p38α, JNK, AKT and HSP27 MAPKs expression pathway. Conclusions: Our data show for the first time that anti-Ribos.P are nephritogenic autoantibodies, as illustrated by in-vitro and in-vivo experiments: a) They accelerate the development of glomerulonephritis in lupus prone mice; b) They induce nephritis in naïve mice. c) Anti-Ribos.P Abs trigger MAPKs expression in primary mesangial cells. These data contribute a direct mechanistic link between anti-Ribos.P and nephritis in lupus mice. © 2014 Elsevier Ltd.


Lerner A.,Technion - Israel Institute of Technology | Matthias T.,Aeskukipp Institute
Autoimmunity Reviews | Year: 2015

The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption.The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them.Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression. © 2015.


Lerner A.,Technion - Israel Institute of Technology | Matthias T.,Aeskukipp Institute
Autoimmunity Reviews | Year: 2015

Rheumatoid arthritis (RA) and celiac disease (CD) belong to the autoimmune disease family. Despite being separate entities they share multiple aspects. Epidemiologically they share comparable incidence environmental influences, associated antibodies and a recent incidental surge. They differ in their HLA pre-dispositions and specific predictive and diagnostic biomarkers. At the clinical level, celiac disease exhibits extra-intestinal rheumatic manifestations and RA gastrointestinal ones. Small bowel pathology exists in rheumatic patients. A trend towards responsiveness to a gluten free diet has been observed, ameliorating celiac rheumatic manifestations, whereas dietary interventions for rheumatoid arthritis remain controversial.Pathophysiologically, both diseases are mediated by endogenous enzymes in the target organs. The infectious, dysbiotic and increased intestinal permeability theories, as drivers of the autoimmune cascade, apply to both diseases.Contrary to their specific HLA pre-disposition, the diseases share multiple non-HLA loci. Those genes are crucial for activation and regulation of adaptive and innate immunity. Recently, light was shed on the interaction between host genetics and microbiota composition in relation to CD and RA susceptibility, connecting bugs and us and autoimmunity.A better understanding of the above mentioned similarities in the gut-joint inter-relationship, may elucidate additional facets in the mosaic of autoimmunity, relating CD to RA. © 2015 Elsevier B.V.

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