Over-expression of paneth cell-derived anti-microbial peptides in the gut of patients with ankylosing spondylitis and subclinical intestinal inflammation.
OBJECTIVE
Subclinical gut inflammation has been demonstrated in patients with AS. Altered expression of paneth cell (PC) anti-microbial peptides have been reported in the inflamed ileum of patients with Crohn's disease (CD). Here, we investigated the expression of PC-derived peptides in subclinical gut inflammation in AS.


METHODS
Multiple adjacent mucosal biopsies from terminal ileum were obtained from 25 patients with AS, 30 CD and 15 healthy controls (HCs). Expression of human α-defensin 5 (HD-5), phospholipase A2 (PLA2), lysozyme and SOX-9 molecules was assessed by quantitative Taqman RT-PCR on mucosal samples. Immunohistochemistry with anti-human HD-5 antibody and genotyping of relevant NOD2 mutations was also performed.


RESULTS
HD-5, PLA2 and lysozyme transcript levels were strongly increased in AS and CD with similar degrees of intestinal inflammation when compared with normal controls. Immunohistochemical evaluation showed a normal number of PCs in both AS patients with chronic gut inflammation and CD patients with less-inflamed ileal samples. Conversely, CD patients with higher degree of gut inflammation had a reduced number of PCs and low expression levels of HD-5.


CONCLUSIONS
In this study, we provide evidence that over-expression of PC-derived anti-microbial peptides occurs in the ileum of AS patients with subclinical gut inflammation, likely representing an important early alteration of the mucosal innate immune component and intestinal host defence in AS.
Ciccia
Francesco
F
Dipartimento Biomedico di Medicina Interna e Specialistica, Divisione di Reumatologia, Università di Palermo, Palermo, Italy.
Bombardieri
Michele
M
Rizzo
Aroldo
A
Principato
Alfonso
A
Giardina
Anna R
AR
Raiata
Francesca
F
Peralta
Sergio
S
Ferrante
Angelo
A
Drago
Sandro
S
Cottone
Mario
M
Pitzalis
Costantino
C
Triolo
Giovanni
G
D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005759:Gastroenteritis / Q000378:metabolism*; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019879:Paneth Cells / Q000378:metabolism*; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D023181:Antimicrobial Cationic Peptides