Abstract | Kronična upalna crijevna bolest je naziv za skupinu idiopatskih bolesti tankog i
debelog crijeva. Tu ubrajamo Crohnovu bolest i ulcerozni kolitis. Ukoliko se unatoč iscrpnoj
dijagnostici konačna dijagnoza crijevne bolesti ne može dokazati, govorimo o
interdeterminantnom kolitisu. U današnje vrijeme sve je viša incidencija ovih bolesti,
posebice u zemljama zapadne Europe. Brojne se teorije i čimbenici navode kao mogući
okidači za razvoj ovih bolesti, no dosad još ništa nije dokazano. Postoje broje patohistološke i
kliničke sličnosti no i značajne razlike.
Dendritične stanice su dio imunološkog sustava. Riječ je o antigen prezentirajućim
stanicama koje sudjeluju u kontroli imunološkog odgovora, a nalaze se u krvi i brojnim
limfatičnim tkivima. S obzirom da je sluznica crijeva trajno izložena tvarima iz vanjskog
svijeta nužan je stalan i uravnotežen imunološki odgovor. Upravo ovu funkciju obavljaju
dendritične stanice. Danas se u brojnim istraživanjima nastoji objasniti način kojim
disfunkcija dendritičnih stanica utječe na razvoj Crohnove bolesti i ulceroznog kolitisa.
Naime, u obje bolesti sluznica crijeva je upalno promijenjena, čime su dendritične stanice
trajno izložene velikim količinama antigena. Pretpostavlja se da to dovodi do nekontroliranog
imunološkog odgovora u genetski osjetljivog domaćina. Postoje brojni biljezi kojim
opisujemo raznolike populacije i subpopulacije dendritičnih stanica. Jedan od tih je protein
S100.
Cilj ovog rada bio je odrediti udio Crohnove bolesti, ulceroznog kolitisa i
nedeterminiranog kolitisa te prosječnu dob i spol u pedijatrijskih bolesnika s idiopatskom
bolesti crijeva čiji su bioptički uzorci korišteni u radu, opisati patohistološke promjene,
odrediti prisutnost i lokalizaciju S100 pozitivnih dendritičnih stanica u bioptičkim uzorcima
sluznice crijeva pedijatrijskih bolesnika s idiopatskom bolesti crijeva. Istraživanje je
provedeno na 36 bioptičkih uzoraka crijeva bolesnika koji su vremenskom razdoblju od 2002.
godine do 2011. godine liječeni u Klinici za pedijatriju KBC-a Split od idiopatske bolesti
crijeva. Bioptički uzorci sluznice tankog ili debelog crijeva zaprimljeni su na Klinički zavod
za patologiju, sudsku medicinu i citologiju KBC Split i fiksirani u 4%-tnom
paraformaldehidu, uklopljeni u parafin, izrezani na polutanke rezove i bojani primjenom
imunohistokemijske metode s primarnim protutijelom na S100.
Od pedijatrijskih bolesnika s idiopatskom bolesti crijeva čiji su bioptički uzorci
korišteni u radu udio bolesnika s Crohnovom bolesti je niži od udjela oboljelih od ulceroznog
kolitisa. Prosječna dob pedijatrijskih bolesnika u slučaju Crohnove bolesti 18,4 godine, a u slučaju ulceroznog kolitisa 18,6 godina. Više bioptiranih bolesnika s Crohnovom bolešću je
bilo muškoga spola, a s ulceroznim kolitisom ženskog spola. Patohistološka promjena nađena
u svim uzorcima bolesnika i s Crohnovom bolesti i s ulceroznim kolitisom je upalni infiltrat.
Intraepitelni granulociti, kriptalni apscesi i reparatorno-degenerativne promjene epitela su
prisutni u većem postotku u uzorcima bolesnika s ulceroznim kolitisom. Samo u uzorcima
oboljelih od Crohnove bolesti nađeni su granulomi i ulceracija sluznice. S100 pozitivne
dendritične stanice su prisutne u sluznici crijeva kao pojedinačne te u nakupinama, a
lokalizirane su subepitelno, u lamini propriji i limfatičnim folikulima crijeva. S100 pozitivne
dendritične stanice nađene su subepitelno samo u uzorcima oboljelih od ulceroznog kolitisa,
dok u lamini propriji crijeva veći postotak pojedinačnih S100 pozitivnih dendritičnih stanica
nađen je u uzorcima oboljelih od Crohnove bolesti, dok su nakupine S100 pozitivnih
dendritičnih stanica bile nešto brojnije u uzorcima oboljelih od ulceroznog kolitisa.
S obzirom na sve višu incidenciju i zahvaćenost pedijatrijske populacije istraživanja
patogeneze crijevne bolesti, u kojoj sve značajniju ulogu imaju istraživanja dendritičnih
stanica, mogao bi doprinijeti razumijevanju ovih bolesti, unaprijediti terapiju te poboljšati
kvalitetu života i odrastanje ovih bolesnika. |
Abstract (english) | Chronic inflammatory bowel disease is the name for a group of idiopathic disorders of
the small and large intestine. These include Crohn's disease and ulcerative colitis. If despite
exhaustive diagnosis definitive diagnosis of intestinal diseases cannot be proven, we are
talking about interdeterminant colitis. At the present time there is a higher incidence of these
diseases, particularly in the countries situated in Western Europe. Numerous theories and
factors are cited as possible triggers for the development of these diseases, but so far nothing
has been proven. There are numerous histopathological and clinical similarities but also there
are significant differences.
Dendritic cells are part of the immune system. They are the antigen-presenting cells
that participate in the control of the immune response, and are found in the blood and the
number of lymphatic tissues. Since the intestinal mucosa is permanently exposed to
substances from the outside world, a constant and necessary balanced immune response is
needed. This function is performed by dendritic cells. Today, a number of researchers are
seeking to explain the way in which dysfunction of dendritic cells influences the development
of Crohn's disease and ulcerative colitis. Namely, in both diseases the mucosa is inflammatory
changed, which makes dendritic cells permanently exposed to large amounts of antigen. It is
assumed that this leads to an uncontrolled immune response in a genetically sensitive host.
There are numerous markers that are used to describe the diverse populations and
subpopulations of dendritic cells. One of these is the S100 protein.
The aim of this study was to determine the proportion of Crohn's disease, ulcerative
colitis and nedeterminant colitis and the average age and gender in pediatric patients with
idiopathic bowel disease whose biopsy specimens were used in the work; write
histopathological changes, determine the presence and localization of S100 positive dendritic
cells in mucosal biopsies samples of pediatric patients with idiopathic bowel disease. The
study was conducted on 36 intestine biopsy samples of patients which were treated for
idiopathic intestinal diseases in the Clinic of pediatrics in the Clinical Hospital Center in Split
over a period from 2002 to 2011. Biopsy samples of the mucosa of the small or large intestine
were received at the Department of Pathology, Forensic medicine and Cytology, Clinical
Hospital Center in Split and fixed in 4% paraformaldehyde, embedded in paraffin, cut into
semi-thin cuts and colored using the immunohistochemical methods with the primary
antibody to S100. From pediatric patients with idiopathic bowel disease whose biopsy samples are used
in this work the number of patients with Crohn's disease is lower than the number of patients
with ulcerative colitis. The average age of pediatric patients in the case of Crohn's disease is
18.4 years, and in the case of ulcerative colitis 18.6 years. More biopsied patients with
Crohn's disease were males, while more patients with ulcerative colitis were females.
Histopathological change found in all samples from patients with Crohn's disease and
ulcerative colitis is an inflammatory infiltrate. Intraepithelial granulocytes, criptal abscesses
and reparatory-degenerative changes in the epithelium are present in a higher percentage of
samples from patients with ulcerative colitis. Granulomas and ulceration of the mucosa were
found only in samples of patients with Crohn's disease. S100 positive dendritic cells are
present in the intestinal mucosa as well as in the individual clusters, and they are subepithelial
localized, in the lamina propria and lymphoid follicles of the intestine.
Given all the higher incidence and involvement of the pediatric population studies of
the pathogenesis of intestinal disease, in which the research of the dendritic cells is becoming
increasingly important, could contribute to the understanding of these diseases, and improve
treatment and quality of life and growth these patients. |