Deiminált fehérjeantigének szerepének vizsgálata a rheumatoid arthritis patomechanizmusában és diagnosztikájában = Study of the role of deiminated protein antigens in the pathomechanism and diagnosis of rheumatoid arthritis

Eredmenyek: 1. Szintetikus peptidekkel igazoltuk, hogy a citrullin nelkulozhetetlen az anti-filaggrin tipusu , rheumatoid arthritisre (RA) specifikus antitestek altal felismert epitopok szerkezeteben. A tobbszorosen citrullinalt szekvenciak reaktivitasa nagyobb, azonban a citrullin kornyezeteben levő aminosavak is szerepet jatszanak az epitop kialakulasaban. Roviditett peptidekkel a filaggrin feherje egyik centralis epitopjat azonositottuk. RA betegek szerumaban es synovialis folyadekaban peptidfelismeres tekinteteben homolog ellenanyagok jelenletet igazoltuk. 2. Osszefuggest talaltunk a RA-re hajlamosito HLA-DRB1 allotipus hordozas es a citrullalt peptid specifikus antitest termeles kozott, mig a PAD4 gen genetikai valtozekonysaga es az anti-CCP antitestek megjelenese nem mutat kapcsolatot a hazai populacioban. 3.A familaris es spodatrikus RA genetikai hattere es patomechanizmusa elterő. 4. Anti-CCP antitestek nem termelődnek polymyalgia rheumaticaban, mely a HLADRB1*0401 csokkent előfordulasaval magyarazhato. 5. Az anti-CCP antitestek előfordulasa RA-s betegeinkben 68,6%, egyeb kotőszoveti betegsegekben 3-5%. | Results: Using synthetic peptides we proved that the presence of citrulline is essential in creation the epitopes targeted by IgG of patients with rheumatoid arthritis (RA). Multiplied substitution of arginies to citrullines increases the reactivity of the epitopes to RA IgG, although the nature of surrounding amino acids play also role in antigenicity. Using shortened citrullinated peptides one of the central epitopes of human filaggrin has been identified. IgG in paired serum and synovial fluid samples of RA patients showed similar recognition pattern, and a highly significant correlation was found between the reactivity of sera and synovial fluids to one of the central epitopes of filaggrin. We found correlation between the presence of HLA-DR SE epitopes and the presence of anti-CCP antibody in patients with RA. No association was found between anti-CCP antibody production and the haplotypes of PAD4 gene in RA patients of Hungarian population. Familiar and sporadic RA differ in their genetic background and pathomechanism. No anti-CCP antibody was found in patients with polymyalgia rheumatica, that could be explained by the decreased frequency of the allele HLA-DR*0401. Prevalence of anti-CCP antibodies in our RA patients was 68,6%, while 3-5% in other connective tissue diseases.