Anti-gliadin antibodies in patients with celiac disease cross-react with enterocytes and human calreticulin.
One of the characteristic features of celiac disease is an increase in anti-gliadin antibodies (Abs). Recently we found that some of the monoclonal Abs to gliadin cross-react with molecules on rat enterocytes. One of these cross-reacting molecules was identified as rat calreticulin. This study shows that the levels of serum IgA Abs to gliadin, rat, and human enterocytes; purified enterocyte antigens; and calreticulin in sera from patients with active disease were significantly higher than in patients on a gluten-free diet and healthy controls (P < 0.001). Anti-gliadin Abs were isolated by affinity chromatography from the sera of six active celiac patients. The reactivity of these anti-gliadin Abs was demonstrated to be significantly higher (P < 0.05) with human enterocytes and human calreticulin than with other antigens tested. Furthermore, using isolated patients' anti-gliadin Abs bound to Sepharose 2B, two main proteins of molecular mass 62 and 66 kDa were purified from a lysate of human enterocytes. The 62-kDa enterocyte antigen was identified as human calreticulin. These findings suggest that anti-gliadin Abs may play a pathogenic role in celiac disease by cross-reacting with enterocytes. Calreticulin in enterocytes may be one of the putative targets for autoimmune reactions.
Tucková
L
L
Division of Immunology and Gnotobiology, Czech Academy of Sciences, Prague, Czech Republic.
Karská
K
K
Walters
J R
JR
Michalak
M
M
Rossmann
P
P
Krupicková
S
S
Verdu
E F
EF
Saalman
R
R
Hanson
L A
LA
Tlaskalová-Hogenová
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood*; D000941:Antigens / Q000276:immunology / Q000302:isolation & purification; D002135:Calcium-Binding Proteins / Q000276:immunology*; D037282:Calreticulin; D002446:Celiac Disease / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000302:isolation & purification; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D012261:Ribonucleoproteins / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D007070:Immunoglobulin A; D012261:Ribonucleoproteins; D005903:Gliadin