Aktivnost serumske dipeptidil-peptidaze IV i ekspresija CD26 antigena na imunokompetentnim ćelijama periferne krvi kod bolesnica sa benignim i malignim promenama dojke
Serum activity of dipeptidyl-peptidase IV and expresiion of CD26 antigen on immunocompetent cells of peripheral blood in patients with benign and malignant breast tumors
Author
Erić-Nikolić, Aleksandra M.
Mentor
Džodić, Radan
Committee members
Juranić, ZoricaGolubičić, Ivana
Rašković, Sanvila

Popadić, Dušan

Metadata
Show full item recordAbstract
Uvod: dipeptidil-peptidaza IV (DPPIV ili CD26) je serin-proteaza koja ima značajnu
ulogu u brojnim biološkim procesima. Kalretikulin je protein koji reguliše brojne važne
ćelijske funkcije. Cilj ovog rada je bio da se odredi serumska aktivnost DPPIV, procenat
CD26+ belih krvnih ćelija i CD26+ limfocita, kao i srednja vrednost intenziteta
fluorescencije ekspresije CD26 na limfocitima u bolesnica sa benignim i malignim
lezijama dojke i u zdravih kontrola i da se utvrdi da li su intenzitet i lokalizacija
povišene ekspresije kalretikulina u tumorskim ćelijama povezani sa povećanjem
humoralnog imuniteta na kalretikulin u ispitivanim grupama. Takođe je analiziran
procenat nekih limfocitnih subpopulacija, CD16+/56+ i CD16+/89+ kod bolesnica sa
malignim i benignim promenama dojke, kao i kod zdravih kontrola.
Metode: Uključeno je 37 bolesnica sa benignim i 68 sa malignim promenama dojke, pre
hirurškog tretmana, kao i 37 zdravih kontrola. Serumska aktivnost DPPIV izmerena je
kolorimetrijskim tes...tom, dok je broj CD26+ćelija određena metodom protočne
citomerije. Citoplazmatska i membranska ekspresija kalretikulina u malignim i
benignim ćelijama parafinskih isečaka utvrđena je imunohistohemijski. Nivoi serumskih
antikalretikulinskih antitela izmereni su ELISA metodom. Procenat ispitivanih
limfocitni subpopulacija određen je metodom protočne citomerije.
Rezultati: Značajan pad u procentu ukupnih CD26+ ćelija ustanovljen je u grupi
bolesnica sa benignim i malignim promenama u poređenju sa zdravim kontrolama.
Intenzitet fluorescencije CD26 ekspresije na limfocitima je značajno niži kod bolesnica sa malignim promenama u poređenju sa zdravim kontrolama. Statistički značajna
razlika je utvrđena u serumskim nivoima antikalretikulinskih IgA antitela između
bolesnica i zdravih kontrola. Relativna učestalost gCD16dim+/56bright+ subpopulacije
imunokompetentnih ćelija je statistički značajno niža u bolesnica sa malignim, ali i
benignim promenama dojke u odnosu na zdrave kontrole; statistički značajno niže
vrednosti su utvrđene i u relativnoj učestalosti tCD16dim+/56bright+ ćelija u bolesnica sa
malignim promenama dojke u odnosu na one u zdravih kontrola; niže vrednosti
procenta gCD16bright+/56dim+imunskih ćelija su takodje karakteristika bolesnica sa
malignim ili benignim promenama u odnosu na zdravie kontrole. Procenat CD89+
imunskih ćelija (uglavnom granulocita) značajno je povišen kako u bolesnica sa malignim promenama tako i u bolesnica sa benignim promenama u odnosu na zdrave
kontrole...
Objective: Dipeptidyl peptidase IV (DPPIV or CD26) is a serine protease which has a
significant role in a variety of biological processes. Calreticulin is a protein which
regulates many important cellular responses. The aim of this work was to determine
serum DPPIV activity as well as the percentage of CD26+ white blood cells and of
CD26+ lymphocytes and the mean fluorescence intensity (MFI) of CD26 expression on
lymphocytes in groups of patients with benign or malignant breast tumors and in
healthy controls and to elucidate whether the intensity and location of calreticulin
overexpression in tumor cells are related to the elevated humoral immunity to
calreticulin in patients with benign or malignant breast disease. It was also analized the
percentage of some subpopulations of lymphocytes, such as: CD16+/56+ i CD16+/89+ in
patients with benign and malignant breast lesions and in healthy controls as well.
Methods: This study involved 37 patients with benign and 68 patients with malignan...t
breast tumors before surgical resection and 37 healthy volunteers. Serum DPPIV
activity was determined by colorimetric test, while CD26+ cells were counted using
flow cytometer. Cytoplasmatic or membranous calreticulin overexpression in malignant
or benign cells in paraffinembedded tissues was determined using
immunohistochemistry. Levels of the serum anti-calreticulin autoantibodies were
detected by ELISA. Percentage of lymphocytes was determined using flow cytometry.
Results: Significant decrease in the percentage of CD26+ total white blood cells was
found in the group of breast cancer patients and in patients with benign breast tumors
compared to healthy people. The MFI of CD26 expression on lymphocytes was significantly lower for cancer patients in comparison to healthy controls. Statistically
significant differences between serum levels of IgA of anti-calreticulin antibodies in
controls and patients with breast tumors, and between controls and patients with
nonmalignant breast diseases were found. It was revealed significant decrease in the
percentage of gCD16dim+/56bright+ cells in patients with benign and malignant breast
lesions, as well as in the of percentage of tCD16dim+/56bright+ in malignant breast lesions
compared with healthy controls. It was also found significant decrease in the of
percentage of gCD16bright+/56dim+ cells in patients with benign and malignant breast
lesions compared with healthy controls. Percentage of CD89+ cells was significant elevated in patients with benign and malignant breast lesions compared to healthy
controls..