5 research outputs found
Gluten Sensitivity Is Associated to Activation of the Innate But Not Adaptive Immune Response to Gluten Exposure
Background: The immune responsiveness to gluten-containing grains represents a complex
process whose establishment and maintenance are not completely elucidated. There are
cases of gluten reaction defined as gluten sensitivity (GS) in which neither an allergic (wheat
allergy) nor an autoimmune [celiac disease (CD)] mechanism can be advocated. Recent
evidences suggest that early changes in intestinal permeability (IP) and activation of both
innate and adaptive immune responses are involved in CD pathogenesis. Conversely, no
data are currently available on the mechanisms leading to GS. Aims: To investigate the
changes in IP, TJ protein genes expression, and innate and adaptive immune responses in
GS. Methods:Biopsy samples were obtained from 28 GS patients(pts), 53 pts with active
CD, 16 patients with CD in remission, and 37 healthy controls (age range: 5 years -50
years). Quantitative gene expression of TJ proteins Claudin (CL) 1, CL2, CL3, CL4, ZO-1,
and TLR1, TLR2 and TLR4, FOXP3, and TGF-β were performed by Real-time PCR. IP was
evaluated by means of the lactulose/mannitol test (LA/MA). The number of intraepithelial
lymphocytes (IELs) were detected with CD3 and TCR-γδ immunostaining and examined by
counting the peroxidase stained cells. ELISA analysis of IL6, IL8, TNFα, was conducted on
PBMC of all patients. Results: Intestinal CL3 and CL4 expressions were significantly increased
in GS subjects compared to CD patients (p<0.01), while no changes in other TJ protein
genes expression were detected. In GS patients, these changes were associated to a lower
IP (0.010±0.008) that inversely correlated to CL4 gene expression (r= -0.6318; p<0.05)
compared to healthy controls (0.018±0.009). Conversely, in CD patients an over-expression
of CL2 was observed that was associated to increased IP (0.053±0.048) and that returned to
baseline following implementation of a gluten free diet. Interestingly, immunohistochemical
examination of biopsy specimen showed a lower number of CD3+IELs in GS pts compared
to active CD pts (27.25/100 and 36.3/100 enterocytes respectively) that correlate with a
MARSH 0-1 lesions, with no changes in TCR-γδ IELs. In a subgroup of GS pts, intestinal
TLR1 and TLR2 expression was increased and these changes were paralleled by increased
production by PBMC of cytokines related to the innate but not adaptive immune responses.
Conclusions: Compared to CD patients, GS subjects showed normal IP and activation of
the innate but not adaptive immune responses. These changes cause only minimal gut
inflammation, suggesting that in GS lack of adaptive immune response involvement prevent
the autoimmune gut insult typical of CD