Enterocyte actin autoantibody detection: a new diagnostic tool in celiac disease diagnosis: results of a multicenter study.
OBJECTIVE
This study describes a new method to detect autoantibodies against actin filaments (AAA) as a serological marker of intestinal villous atrophy (IVA) in celiac disease (CD), and reports the results of an Italian double-blind multicenter study.


METHODS
IgA-AAA were analyzed by immunofluorescence using a newly developed method based on intestinal epithelial cells cultured in presence of colchicine. IgA-AAA were blindly evaluated prospectively in 223 antiendomysial antibody (AEA) and/or antitransglutaminase antibody (TGA) positive subjects and in 78 AEA and TGA negative subjects. IgA-AAA positive patients underwent an intestinal biopsy to confirm the diagnosis. Moreover, IgA-AAA were retrospectively investigated in 84 biopsy-proven CD patients and in 2,000 new consecutively collected serum samples from AEA and TGA negative nonbiopsied subjects.


RESULTS
IgA-AAA were positive in 98.2% of the CD patients with flat mucosa, in 89% with subtotal villous atrophy, and in 30% with partial villous atrophy. IgA-AAA were present in none of the AEA and TGA negative nonbiopsied controls. In AEA and/or TGA positive CD patients IgA-AAA positivity significantly correlated with IVA (p < 0.000 in the prospective study, p = 0.005 in the retrospective study). In the prospective study, the values of sensitivity, specificity, the positive predictive value, the negative predictive value, and the efficiency of the IgA-AAA test to identify patients with IVA were, respectively, 83.9%, 95.1%, 97.8%, 69.2%, and 87.0%. Furthermore, a significant correlation (p < 0.0001) was found between the IgA-AAA serum titre and the degree of IVA (rs 0.56).


CONCLUSIONS
The results of this multicenter study show that the new method for IgA-AAA detection could represent a practical diagnostic tool in AEA and/or TGA positive subjects, which would be especially useful when IVA shows a patchy distribution, when the histological picture is difficult to interpret, or when a biopsy could represent a life-threatening risk.
Department of Biomedical Sciences and Biotechnologies, Second Pediatrics Clinic, Cagliari University, Italy.
M G
MG
Clemente
M P
MP
Musu
R
R
Troncone
U
U
Volta
M
M
Congia
C
C
Ciacci
E
E
Neri
T
T
Not
G
G
Maggiore
P
P
Strisciuglio
G R
GR
Corazza
G
G
Gasbarrini
L
L
Cicotto
G
G
Sole
A
A
Fasano
S
S
De Virgiliis
D000199:Actins / Q000276:immunology* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002446:Celiac Disease / Q000175:diagnosis* / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D020895:Enterocytes / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007223:Infant; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D011503:Transglutaminases / Q000276:immunology
D000199:Actins; D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D011503:Transglutaminases