Clinical, HLA, and small bowel immunohistochemical features of children with positive serum antiendomysium antibodies and architecturally normal small intestinal mucosa.
BACKGROUND
Antiendomysium antibodies have a high sensitivity and specificity for celiac disease. A small percentage of subjects positive for these antibodies have a small intestinal mucosa hitherto considered normal.


OBJECTIVE
The aim of this study was to characterize the clinical, serological, immunogenetic, and immunohistological features of these subjects.


METHODS
From 409 patients who were positive for celiac-related antibodies, we selected 24 (5.9%) patients who had an architecturally normal small intestinal mucosa. One hundred age-matched celiac patients with a "flat" small intestinal mucosa, and 50 age-matched nonceliac children were also studied. The number of CD3+ and gammadelta+ intraepithelial lymphocytes and of CD25+ lamina propria mononuclear cells, and the expression of crypt HLA-DR and lamina propria ICAM-1 were assessed. HLA haplotyping was also performed.


RESULTS
Eleven (45.8%) of the 24 patients had a distinct infiltrative pattern, i.e., an increase in CD3+ intraepithelial lymphocytes (> 2SD of the nonceliac group), whereas 17 (70.8%) had a higher density of intraepithelial gammadelta+ cells. In 17 (70.8%) patients, the number of lamina propria CD25+ cells was increased and/or the expression of ICAM-1 and crypt HLA-DR was enhanced. All 24 patients carried the celiac disease-associated HLA haplotypes. Two of the six patients who remained on a normal diet and underwent a second jejunal biopsy developed villous atrophy.


CONCLUSIONS
Most of the patients with serum antiendomysium antibodies and normal jejunal histology showed immunohistochemical signs of immune activation in the epithelium, lamina propria, and crypts. We recommend that such patients be monitored to assess their progress and to determine whether they need a gluten-free diet.
Paparo
Francesco
F
Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
Petrone
Emma
E
Tosco
Antonella
A
Maglio
Maria
M
Borrelli
Melissa
M
Salvati
Virginia M
VM
Miele
Erasmo
E
Greco
Luigi
L
Auricchio
Salvatore
S
Troncone
Riccardo
R
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002446:Celiac Disease / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003238:Connective Tissue / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007223:Infant; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D007583:Jejunum / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology
D001323:Autoantibodies; D006680:HLA Antigens; D007070:Immunoglobulin A; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins