Epitopes of calreticulin recognised by IgA autoantibodies from patients with hepatic and coeliac disease.
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.
Sánchez
Daniel
D
Department of Immunology, Institute of Microbiology, Czech Academy of Sciences, 142204 Prague, Czech Republic. sanchez@biomed.cas.cz
Tucková
Ludmila
L
Mothes
Thomas
T
Kreisel
Wolfgang
W
Benes
Zdenek
Z
Tlaskalová-Hogenová
Helena
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D037282:Calreticulin / Q000737:chemistry* / Q000276:immunology*; D002446:Celiac Disease / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D019204:GTP-Binding Proteins / Q000276:immunology; D005903:Gliadin / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008107:Liver Diseases / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011994:Recombinant Proteins; D011503:Transglutaminases / Q000276:immunology
D001323:Autoantibodies; D037282:Calreticulin; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins