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Autologous Hematopoietic Stem Cell Transplantation for Crohn’s Disease
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Robert M. Craig, Richard K. Burt
Further support for intestinal flora as a cause of disease is the presence of anti-Saccharomyces cerevisiae antibody (ASCA) in patients with Crohn’s disease. Saccharomyces cerevisiae is Baker’s yeast. Yeast exert a strong adjuvant effect upon dendritic cells resulting in IL-12 production and priming of T cell responses, and are a commonly used assay for demonstrating intact Th1 delayed type hypersensitivity. ASCA may be used as a diagnostic marker to help differentiate Crohn’s disease from ulcerative colitis.28,29 Proliferation assays of peripheral blood lymphocytes incubated with Saccharomyces cerevisiae and pulsed with tritiated thymidine demonstrate a three fold increase in proliferative response from Crohn’s patients compared to normal controls, including healthy normal bakers.30 Pre and post transplant peripheral blood ASCA antibody, T cell proliferative responses, and T cell lines to intact Saccharomyces cerevisiae and/or extracts from Saccharomyces cerevisiae may be generated and analyzed to determine the role of gut flora in causing Crohn’s disease.
Modern Insights into the Aetiology of Inflammatory Bowel Disease
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Dharmaraj Durai, A. Barney Hawthorne
It is possible however that MAP has an indirect pathogenic role.34 MAP expresses the mannose alpha 1, 3 mannose epitope for the anti-Saccharomyces cerevisiae antibody (ASCA), and this can inhibit bactericidal function of macrophages, a defect present in other conditions that produce Crohn’s-like gut inflammation (e.g. chronic granulomatous disease). An acquired defect in phagocytic ability to clear intracellular bacteria could add to genetic defects in autophagy associated with Crohn’s. Mycobacterial DNA within granulomas can alter cytokine function, and mycobacterial antigens could mimic host peptides and cause an autoimmune cross-reactivity that could contribute to tissue damage in genetically susceptible individuals.
Serological antibodies and surgery in a population-based inception cohort of Crohn’s disease patients – the IBSEN study
Published in Scandinavian Journal of Gastroenterology, 2020
Vendel A. Kristensen, Milada Cvancarova, Marte Lie Høivik, Bjørn Moum, Morten H. Vatn
Seroreactivity to specific antigens, both autoantigens and microbial antigens, is seen in subgroups of patients with inflammatory bowel disease (IBD) and have attracted attention as potential non-invasive biomarkers with a diagnostic and prognostic potential. Such antibodies as anti-Saccharomyces cerevisiae antibody (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibody (pANCA) have been widely studied [4]. However, studies have shown diverging results regarding diagnostic specificity and stability of titres over time [5–8], questioning the clinical importance of these antibodies. Studies of both short- and long-term stability of serological antibodies are therefore crucial to estimate the diagnostic significance as well as prognostic impact of such markers. Current guidelines do, so far, not recommend routine analysis of any single serological antibody due to limited diagnostic accuracy [9]. The long-term stability and predictability of such antibodies applied in population-based inception cohorts require further studies. Also, panels combining several antibodies in a combination model or a risk matrix model may improve the clinical use as predictors of disease outcome in IBD.
IgA nephropathy in a child: Crohn’s disease-associated or adalimumab induced?
Published in Current Medical Research and Opinion, 2022
Francesco Graziano, Martina Busè, Nicola Cassata, Vincenzo Luca Lentini, Michele Citrano
A nine-year-old boy, negative family history for IBD and kidney diseases, because of persistent abdominal pain, diarrhea associated with fever and weight loss, was admitted at our Unit. The first laboratory tests performed showed Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP) two times greater than the normal range. Hepatic and renal function, celiac disease markers and urinalysis were normal. Anti-Saccharomyces cerevisiae antibody (ASCA) IgG value was 126 U/ml (normal 0–20 U/mL), tests for antinuclear antibody (ANA), anti double–stranded DNA (anti ds-DNA) and perinuclear antineutrophil cytoplasmic autoantibodies (p-ANCA) were negative. Faecal calprotectin (FC) was 600 mg/kg/stools (normal 0–50 mg/kg/stools).
Detection of a novel antigen for Crohn’s disease
Published in Scandinavian Journal of Gastroenterology, 2021
Yarong Wei, Tingting Chen, Wu Yang, Huihui Li, Chen Fang, Qiuyuan Liu, Yonghao Chen, Qiao Mei
Anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) have been widely used in serological studies of patients with IBD. ANCA is associated with neutrophil-mediated inflammation, which is divided into two subtypes by indirect immunofluorescence (IIF), namely cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA). Atypical pANCA is related to the cross reaction between mycobacteria and histone H1 [6], which is described in 41–73% of UC patients [7]. ASCA is a specific antibody to Saccharomyces cerevisiae cell wall mannose, being tested in 29–69% of CD patients [7]. Sensitivity and specificity of pANCA to identify UC and CD were 52 and 91%, and sensitivity and specificity of ASCA to identify UC and CD were 37–72% and 82–100%, respectively [7]. Combined application of ASCA and pANCA showed good specificity in the differential diagnosis of UC and CD, but showed insufficient sensitivity [8]. Although ANCA and ASCA may be helpful in diagnosing IBD, their role in IBD remains controversial. It was previously reported that the measurement of ASCA is less sensitive to CD and less effective in differentiating CD from UC when the diseases were limited to the colon [8]. A prospective study suggested that almost half of unclassified IBD patients examined negative for ASCA and pANCA [9]. The positivities of pANCA and ASCA vary among different races, pANCA exhibits higher positivity in Caucasian UC compared with Chinese UC and the positivity of ASCA IgA in Chinese CD is lower than Caucasian CD [10]. Furthermore, other serological markers such as anti-glycoprotein 2 (anti-GP2), anti-Pseudomonas fluorescens-associated sequence I2 (anti-I2) and anti-outer membrane porin C of Escherichia coli (anti-OmpC) showed low sensitivity [5]. Accordingly, a single antibody satisfactory to the diagnosis of IBD has not been identified, exploring more accurate and efficient serological biomarkers is still a very important focus of IBD research.