Calreticulin (CRT) was identified as a frequent target of serum autoantibodies (Ab) in various diseases, but anti-CRT Ab of IgA isotype were described only in coeliac (CLD) and some hepatic diseases. Employing ELISA with recombinant CRT we found significantly higher (P<0.001) levels of IgA anti-CRT Ab in sera of patients with primary biliary cirrhosis (PBC) (77.6+/-8.9 AU/mean+/-SE), autoimmune hepatitis (AIH) (105.1+/-9.2 AU) and alcoholic liver cirrhosis (ALC) (193.5+/-21.0 AU) relative to healthy controls (38.6+/-2.0 AU). The levels of IgG anti-CRT Ab in sera of patients with PBC (59.5+/-3.4 AU), AIH (89.7+/-7.9 AU) and ALC (86.4+/-6.2 AU) were also significantly increased (P<0.001) when compared with controls (38.5+/-2.1 AU). Pepscan technique with decapeptides of CRT (each overlapping by eight amino acids) revealed antigenic epitopes of this molecule recognised by IgA Ab of almost all tested patients-KGKNVLINKD and QVKSGTIFDNFL. We also identified disease specific antigenic epitopes on CRT molecule, predominantly recognised by IgA Ab of patients suffering from a particular disease: GGYVKLFPNS and YVKLFPNSLD in AIH (83%, 92% of patients), GLQTSQDARF and EQRLKEEEED in CLD (both 75%) and ASKPEDWDER in ALC (67%). Identification of disease specific CRT epitopes contributes to clarification of autoreactivity against this molecule.

Department of Immunology Institute of Microbiology Czech Academy of Sciences 142204 Prague Czech Republic

References provided by Crossref.org

Contribution of Infectious Agents to the Development of Celiac Disease

Celiac Disease and Liver Disorders: From Putative Pathogenesis to Clinical Implications

Celiac disease markers in patients with liver diseases: a single center large scale screening study

Calreticulin is a B cell molecular target in some gastrointestinal malignancies

Anti-calreticulin immunoglobulin A (IgA) antibodies in refractory coeliac disease