Immunoregulatory pathways are active in the small intestinal mucosa of patients with potential celiac disease.
OBJECTIVE
Potential celiac disease (CD) relates to subjects with a normal small intestinal mucosa who are at increased risk of developing CD as indicated by positive CD-associated serology. The objective of this study was to investigate in the small intestinal mucosa of such patients the state of immunological activation with special emphasis on immunoregulatory circuits.


METHODS
Duodenal biopsies from active CD (n=48), potential CD (n=58), and control patients (n=45) were studied. RNA expression for interferon γ (IFNγ) and interleukin-10 (IL-10) were quantified by real-time quantitative PCR. The percentage of CD4+CD25+Foxp3+ T regulatory cells (Foxp3+Tregs) was determinated by flow cytometry and the number of Foxp3+ and IL-15+ cells by immunohistochemistry. Furthermore, we analyzed the suppressive function of CD4+CD25+ T cells, isolated from potential CD biopsy samples, as well as the effect of IL-15, on autologous peripheral blood responder CD4+CD25- T cells.


RESULTS
In potential CD patients with Marsh 1 lesion, IFNγ-RNA expression was significantly less than in active, but enhanced if compared with potential CD patients with Marsh 0 lesion and with controls (P<0.001). The number of IL-15+ cells in subjects with potential CD was increased in comparison with controls (P<0.05), but lower than active CD (P<0.01). IL-10-RNA expression was upregulated in Marsh 0 potential CD patients if compared with those with Marsh 1 lesion (P<0.01) and controls (P<0.001), whereas there were no differences with active CD. The ratio IL-10/IFNγ reached the highest value in Marsh 0 potential CD compared with the other groups (P<0.05). The percentage of Foxp3+Tregs was also higher in potential CD compared with controls (P<0.05), although it was lower than in active CD (P<0.01). In co-culture assay, intestinal CD4+CD25+ T cells from potential CD patients exerted suppressive effects on T responder cells, and their activity was not impaired by IL-15.


CONCLUSIONS
Potential CD patients show a low grade of inflammation that likely could be due to active regulatory mechanisms preventing the progression toward a mucosal damage.
Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
Melissa
M
Borrelli
Virginia M
VM
Salvati
Mariantonia
M
Maglio
Delia
D
Zanzi
Katia
K
Ferrara
Sara
S
Santagata
Domenico
D
Ponticelli
Rosita
R
Aitoro
Giuseppe
G
Mazzarella
Giuliana
G
Lania
Carmen
C
Gianfrani
Renata
R
Auricchio
Riccardo
R
Troncone
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002446:Celiac Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology*; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D051858:Forkhead Transcription Factors; D019409:Interleukin-15; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10