Imunoreaktivnost na proteine hrane kod pacijenata sa ranim reumatoidnim artritisom

Abstract

Uloga izmenjene crevne mukoze kao osnove nastanka autoimunosti u reumatoidnom artritisu (RA) još uvek nije razjašnjena. Kod bolesnika sa poodmaklim RA se mogu otkriti antitela na različite antigene iz hrane. Poseban značaj pridaje se IgG klasi ovih antitela jer aktivacija njihovih receptora (CD16/ FcγIIIR) na ćelijama imunskog sistema može imati veoma raznovrsne efekte. Nije poznato zašto postoji povišena imunoreaktivnost na antigene hrane kod bolesnika sa RA. Kao jedan od mogućih uzroka povišene imunoreaktivnosti na svakodnevne antigene iz hrane spominje se i enzim dipeptidil peptidaza IV (DPPIV). Ovaj enzim menja aktivnost biološki aktivnih peptida, a kao jedna od najvažnijih uloga ove peptidaze navodi se njen doprinos aktivaciji T limfocita i pokretanje imunskog odgovora. Brojna literatura opisuje serumsku aktivnost i ekspresiju DPPIV u hroničnom reumatoidnom artiritsu, ali nema puno podataka o ulozi ovog enzima u patogenezi ranog RA. Rad je imao za cilj da se prouči moguća povezanost između humoralne i ćelijske imunoreaktivnosti na antigene prisutne u namirnicama (glijadin, proteini kravljeg mleka i fitohemaglutinin) sa aktivnošću bolesti u obolelih od ranog, nelečenog RA. Dodatno, cilj je bio i da se odredi serumska aktivnost i ekspresija DPPIV na mononuklearnim ćelijama krvi kod pacijenata sa RA i da se utvrdi njihova moguća povezanost sa kliničkim pokazateljima bolesti. Ispitivana je i ekspresija IgG receptora na površini imunokompetentnih ćelija. Studija preseka obuhvatila je 50 bolesnika sa ranim, nelečenim RA, kao i 100 osoba u tri kontrolne grupe. U prvoj kontrolnoj grupi bilo je 30 obolelih od degenerativnih bolesti zglobova i kičme, uskladjenih po polu i po starosti sa obolelima od RA. Drugu kontrolnu grupu je činilo 40 zdravih ispitanika, a treću 30 bolesnika sa dugotrajnim RA (bolest trajala duže od 5 god) koja je učestvovala samo u ispitivanju ekspresije i serumske aktivnosti DPPIV...

The potential role of changed gut mucosa as a basis for development of autoimmunity in rheumatoid arthritis (RA) has been assessed, but still remains unclear. Antibodies to food antigens were detected in chronic RA, with the special emphasis on IgG class of antibodies, because the activation of their receptors (CD16/FcγIIIR) on many different immune cells can result in various effects. As a potential cause of this immunoreactivity to food antigens, the enzyme dipeptidyl peptidase IV (DPPIV/CD26) is mentioned. DPPIV/CD26 changes activity of biologically active peptides, but one of the most important roles of this enzyme is activation of T lymphocytes and immune regulation. The majority of published data deals with chronic, established RA disease. However, little is known about the possible role of DPPIV/CD26 in the pathogenesis of early RA. The aim of this study was to investigate possible relationship between humoral/cellular immunity to food antigens and disease activity in treatment naive patients with early RA (eRA). Moreover, the aim of this study was to determine the serum activity of DPPIV, its expression on peripheral blood mononuclear cells (PBMC) and to assess possible correlations with disease activity (DAS28) in untreated patients with eRA. Furthermore, expression of CD16 on immunocompetent cells of peripheral blood and its possible relation to food antigens was examined. Study included 50 patients with early, untreated RA, and 100 persons in three control groups. First control group consisted of 30 patients with osteoarthritis, matched by age and gender. Second control group included 40 healthy volunteers and third control group consisted of 30 patients with chronic RA (tested only for DPPIV serum activity and expression). ELISA tests were used to determine the levels of IgA, IgG and IgM antibodies to gliadin and cow’s milk proteins (CMP), MTT test was used for the determination of the stimulation of lymphocyte proliferation. Determination of subpopulations (CD16, CD56, CD26) of immunocompetent cells was performed by flow cytometry. Serum activity of DPPIV was determined by the direct photometric method...