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Laass M.W.,TU Dresden | Roggenbuck D.,TU Brandenburg | Roggenbuck D.,GA Generic Assays GmbH | Conrad K.,TU Dresden
Autoimmunity Reviews | Year: 2014

Crohn's disease (CrD) is a chronic relapsing inflammatory bowel disease (IBD) potentially affecting any portion of the gastrointestinal tract from the mouth to the anus. CrD usually manifests between 15 and 30. years of age and presents typically with abdominal pain, fever, bloody or non-bloody diarrhoea, and weight loss. Paediatric patients may show failure to thrive, growth impairment, and delayed puberty additionally. Extraintestinal manifestations like arthritis, uveitis, and erythema nodosum are diagnosed in almost half of the patients. CrD is characterized by a discontinuous and ulcerous transmural inflammation often involving the ileocaecal region and leading to a stricturing or even fistulising phenotype in up to 50% of patients finally. Incidence and prevalence of CrD have been rising worldwide over the past decades. Although many details of the pathophysiology of CrD have been elucidated, no common aetiopathogenic model exists for all forms of CrD, presenting more an umbrella term for a phenotypically and genotypically heterogeneous clinical condition. In CrD, we see an inappropriate response of the innate and/or adaptive immune system to the intestinal microbiota in genetically predisposed individuals. The diagnosis of CrD is based mainly on patient's history and clinical examination and supported by serologic, radiologic, endoscopic, and histologic findings. Antibodies to Saccharomyces cerevisiae and autoantigenic targets such as glycoprotein 2 may aid in differentiating CrD from UC. Their single use, however, is limited by low sensitivity requiring antibody profiling for an appropriate serologic diagnosis. This review focuses on diagnostic and classification criteria of CrD. © 2014 Elsevier B.V. Source

Conrad K.,TU Dresden | Roggenbuck D.,TU Brandenburg | Roggenbuck D.,GA Generic Assays GmbH | Laass M.W.,TU Dresden
Autoimmunity Reviews | Year: 2014

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD) characterised by superficial mucosal ulceration, rectal bleeding, diarrhoea, and abdominal pain. In contrast to Crohn's disease (CrD), UC is restricted to the colon and the inflammation is limited to the mucosal layer. Classic UC affects the colon in a retrograde and continuous fashion starting from the rectum and extending proximally. Dependent on the anatomic extent of involvement, UC can be classified as proctitis, left-sided colitis, or pancolitis. Inflammatory arthropathies and primary sclerosing cholangitis (PSC) are the most common and clinically most important extraintestinal manifestations of UC. The aetiopathogenesis of UC is incompletely understood, but immune-mediated mechanisms are responsible for dysregulated immune responses against intraluminal antigens in genetically predisposed individuals. The diagnosis is based on the history, as well as clinical, radiological, endoscopic and histological features. Autoantibodies, mainly antineutrophil cytoplasmic antibodies (ANCA) and anti-goblet cell antibodies (GAB) may be helpful in the early diagnosis of UC and in differentiating it from CrD. © 2014 Elsevier B.V. Source

Conrad K.,TU Dresden | Roggenbuck D.,GA Generic Assays GmbH | Reinhold D.,Otto Von Guericke University of Magdeburg | Sack U.,University of Leipzig
Autoimmunity Reviews | Year: 2012

Disease associated autoantibodies (AAB) are important biomarkers not only to confirm the diagnosis of the respective systemic autoimmune disease but also to diagnose the disease at very early stages (mono- or oligosymptomatic manifestations) or to diagnose the respective disease without the typical clinical manifestations (atypical forms). A confirmation of the diagnosis in early stages is required, if patients should benefit from early therapeutic intervention. Furthermore, AAB determinations are used for prognostic purposes and for monitoring of disease activity or response to therapy. For the advancement of autoantibody diagnostics in clinical practice the following aspects have to be considered: (i) The search for novel clinically relevant AAB and the identification of autoantigenic targets of AAB broadened the spectrum of autoimmune diagnostics and permit the diagnosis of former idiopathic diseases. (ii) To obtain steady diagnostic variables of clinically relevant AAB, the evaluation studies have to be standardized. (iii) Several special features and novel developments of autoantibody diagnostics make correct interpretation of antibody test results increasingly difficult. (iv) Beside standardization of AAB detection methods and quality management efforts the improvement of autoantibody diagnostics depends on further development of diagnostic algorithms including cost-effective multiparametric analyses. © 2011 Elsevier B.V. Source

Zophel K.,TU Dresden | Roggenbuck D.,GA Generic Assays GmbH | Schott M.,Heinrich Heine University Dusseldorf
Autoimmunity Reviews | Year: 2010

Commercial assays to measure thyroid stimulating hormone (TSH) receptor (TSHR) autoantibodies (TRAb) have been available for the serological diagnosis of autoimmune thyroid diseases (AITD) for several years. The widespread assessment of this parameter has identified Graves' disease (GD) as a common organ-specific autoimmune disease. Within the present article we aim to review immunobiological and epidemiological aspects as well as diagnostic methods available for the detection of TRAb. Over the last decade, TRAb detection in GD became more sensitive since TRAb assays were being largely improved by named research groups. Therefore, functional assay (fas) and diagnostic sensitivity of current TRAb assays will be discussed. Within the second part of this review we will focus on clinical applications of TRAb measurement for outcome prediction of GD as well as the importance of this method to distinguish GD from other AITD. © 2010 Elsevier B.V. Source

Roggenbuck D.,TU Brandenburg | Roggenbuck D.,GA Generic Assays GmbH | Reinhold D.,Otto Von Guericke University of Magdeburg | Schierack P.,TU Brandenburg | And 3 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2014

Crohn's disease (CrD) and ulcerative colitis (UC) are the main inflammatory bowel diseases (IBD). IBDspecific humoral markers of autoimmunity in the form of autoantibodies have been reported first in the late 1950s by demonstrating the occurrence of autoimmunity in UC, while humoral autoimmunity in CrD can be traced back to the 1970s. Ever since, the pathophysiological role of autoimmune responses in IBDs has remained poorly understood. Notwithstanding, autoreactive responses play a major role in inflammation leading to overt IBD. In CrD, approximately 40% of patients and <20% of patients with UC demonstrate loss of tolerance to antigens of the exocrine pancreas. Glycoprotein 2 (GP2) has been identified as a major autoantigenic target of the so-called pancreatic antibodies. The previously unsolved contradiction of pancreatic autoreactivity and intestinal inflammation in IBD was elucidated by demonstrating the expression of GP2 at the site thereof. Intriguingly, GP2 has been reported to be a receptor on microfold cells of intestinal Peyer's patches, which are believed to represent the origin of CrD inflammation. The development of immunoassays for the detection of antibodies to GP2 has paved the way to investigate the association of such antibodies with the clinical phenotype in CrD. Given the recently discovered immunomodulating role of GP2 in innate and adaptive intestinal immunity, this association can shed further light on the pathophysiology of IBD. In this context, the association of anti-GP2 autoantibodies as novel CrD-specific markers with the clinical phenotype in CrD will be discussed in this review. Source

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