[Possible pathogenic role of vascular, immunologic and genetic factors in certain gastroenterologic disorders]

Mária Papp
Orvosi Hetilap 2008 November 30, 149 (48): 2269-76
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.

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