Author/Editor		Čurin-Šerbec, Vladka
Title		Monoclonal antibodies against TNF-alpha in diagnostics and therapy
Translated title		Monoklonska protitelesa proti TNF-alfa v diagnostiki in terapiji
Type		članek
Source		Med Razgl
Vol. and No.		Letnik 43, št. Suppl 5
Publication year		2004
Volume		str. 29-32
Language		eng
Abstract		The importance of cytokines in connection with malignant diseases and autoimmune diseases such as rheumatoid arthritis (RA) is well established. On the other hand, the role and the importance of their natural inhibitors is not as clear yet. Tumor necrosis factor alpha (TNF-alpha) is a member of the cytokine family and is produced by stimulated mononuclear cells and certain fibroblasts. It appears in the form of a homotrimer molecule, which is biologically active. TNF-alpha has been discovered due to its ability to provoke tumor necrosis. It is cytotoxic and can in some cases activate proinflammatory factors. In addition to TNF-alpha, its two natural inhibitors, p55 (TNFRI) and p75 (TNFRII), are also produced. Both inhibitors can be found in human sera and urine, in the soluble form. Serum concentrations of these proteins can be determined using enzyme-linked immunosorbent assay (ELISA), based on monoclonal antibodies (MAb) against TNF-alpha and its soluble receptors in order to establish their diagnostic and/or prognostic value. Additionally, humanization of MAbs against TNF-alpha has led to successful treatment of some diseases, especially RA.
Summary		Citokini igrajo pomembno vlogo pri različnih oblikah rakavih obolenj in avtoimunskih boleznih (npr. revmatoidnem artritisu, RA), še vedno pa ni popolnoma pojasnjeno, kakšna je vloga njihovih naravnih inhibitorjev. Faktor tumorske nekroze alfa (TNF-alfa) je citokin, ki ga sintetizirajo in izločajo mononuklearne fagocitne celice in nekateri fibroblasti. Pojavlja se v obliki homotrimerne molekule, ki je biološko aktivna. Posledice delovanja TNF-alfa so lahko hemoragična nekroza tumorjev, citotoksičnost, aktivacija provnetnih faktorjev in druge. Povišane koncentracije TNF-alfa zaznamo pri različnih vnetjih kot posledico povečane sinteze in izločanja iz aktiviranih makrofagov in limfocitov. S TNF-alfa se izražata tudi njegova naravna inhibitorja, p55 (TNFRI) in p75 (TNFRII), ki ju v serumu najdemo tudi v topni obliki. Z encimsko imunskimi testi ELISA, razvitimi na osnovi monoklonskih protiteles (MPt) proti TNF-alfa in topnima receptorjema, lahko določamo serumske koncentracije omenjenih proteinov pri različnih boleznih ter poskušamo določiti njihovo diagnostično oz. prognostično vrednost. Humanizirana MPt proti TNF-alfa so se izkazala tudi za zelo uspešna pri zdravljenju nekaterih bolezni, predvsem RA.
Descriptors		AUTOIMMUNE DISEASES TUMOR NECROSIS FACTOR ANTIBODIES, MONOCLONAL ENZYME-LINKED IMMUNOSORBENT ASSAY ONCOGENE PROTEINS V-FOS