Calreticulin, upon translocation to the cell surface, plays a critical role in the recognition of tumour cells and in experimentally induced cellular anti-tumour immunity. However, less is known about anti-calreticulin antibodies and their role in malignancies. Using enzyme-linked immunosorbent assay (ELISA), we found immunoglobulin (Ig)A and/or IgG anti-calreticulin antibodies in sera of approximately 63% of patients with hepatocellular carcinoma (HCC), 57% of patients with colorectal adenocarcinoma (CRA) and 47% of patients with pancreatic adenocarcinoma (PACA), while healthy controls, patients with viral hepatitis C and with chronic pancreatitis reached only 2%, 20% and 31% seropositivity, respectively. We found significantly elevated mean levels of IgA anti-calreticulin antibodies (P < 0.001) in patients with HCC (78.7 +/- 52.3 AU, mean +/- standard deviation), PACA (66.5 +/- 30.9 AU) and CRA (61.8 +/- 25.8 AU) when compared to healthy controls (41.4 +/- 19.2 AU). Significantly elevated mean levels of IgG anti-calreticulin antibodies (P < 0.001) were detected in patients with HCC (121.9 +/- 94.2 AU), gall bladder adenocarcinoma (118.4 +/- 80.0 AU) and PACA (88.7 +/- 55.6 AU) when compared to healthy controls (56.7 +/- 22.9 AU). Pepscan analysis revealed a large number of antigenic epitopes of calreticulin recognized by both IgA and IgG antibodies of patients with HCC and PACA, indicating robust systemic immune response. Moreover, significantly elevated levels of antibodies against peptide KGEWKPRQIDNP (P < 0.001) in these patients, tested by ELISA, confirmed the distinct character of antibody reactivity against calreticulin. The high occurrence and specificity of serum anti-calreticulin autoantibodies in the majority of patients with some gastrointestinal malignancies provide the evidence for their possible clinical relevance.

• MeSH
• adenokarcinom krev   imunologie   MeSH
• autoantigeny imunologie   MeSH
• autoprotilátky krev   imunologie   MeSH
• B-lymfocyty imunologie   MeSH
• chronická hepatitida C krev   imunologie   MeSH
• dospělí MeSH
• ELISA MeSH
• epitopy imunologie   MeSH
• hepatocelulární karcinom krev   imunologie   MeSH
• imunoglobulin A krev   imunologie   MeSH
• imunoglobulin G krev   imunologie   MeSH
• kalretikulin imunologie   MeSH
• kolorektální nádory krev   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové proteiny imunologie   MeSH
• nádory jater krev   imunologie   MeSH
• nádory slinivky břišní krev   imunologie   MeSH
• nádory žlučníku krev   imunologie   MeSH
• pankreatitida krev   imunologie   MeSH
• protilátky nádorové krev   imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• specificita protilátek MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• autoantigeny MeSH
• autoprotilátky MeSH
• epitopy MeSH
• imunoglobulin A MeSH
• imunoglobulin G MeSH
• kalretikulin MeSH
• nádorové proteiny MeSH
• protilátky nádorové MeSH

Refractory coeliac disease (RCD) is a very rare and dangerous form of CD, in which gluten-free diet loses its therapeutic effect and the damage of intestinal mucosa persists. Because of the adherence to the diet, serological markers of CD [immunoglobulin A (IgA) antibodies against gliadin, tissue transglutaminase (tTG) and endomysium] are often missing in RCD patients. We found substantially elevated levels of IgA anti-calreticulin (CRT) antibodies in the sera of almost all RCD patients tested. These sera were negative for IgA antibodies to gliadin and tTG and only some of them showed IgA antibodies to enterocytes. Analysis of patients' IgA reactivity to CRT fragments (quarters and halves) by Western blotting revealed differences in the specificity of IgA antibodies between RCD and CD patients. We therefore used the Pepscan technique with synthetic overlapping decapeptides of CRT to characterize antigenic epitopes recognized by serum IgA antibodies of RCD patients. Employing this method we demonstrated several dominant antigenic epitopes recognized by IgA antibodies of RCD patients on the CRT molecule. Epitope GVTKAAEKQMKD was recognized predominantly by serum IgA of RCD patients. Our results suggest that testing for serum IgA antibodies against CRT and its selected peptide could be a very useful tool in RCD differential diagnosis.

• MeSH
• bezlepková dieta škodlivé účinky   MeSH
• celiakie krev   diagnóza   imunologie   MeSH
• ELISA MeSH
• enterocyty chemie   imunologie   MeSH
• gliadin krev   imunologie   MeSH
• imunoglobulin A krev   imunologie   MeSH
• kalretikulin krev   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protilátky anti-idiotypické krev   imunologie   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• transglutaminasy krev   imunologie   MeSH
• western blotting MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gliadin MeSH
• imunoglobulin A MeSH
• kalretikulin MeSH
• protilátky anti-idiotypické MeSH
• transglutaminasy MeSH