Background: The activation of NLRP3-inflammasome may contribute to inflammatory processes in rheumatoid arthritis (RA). Functional polymorphisms in the genes coding for its components NLRP3 and CARD8 were associated with a proinflammatory phenotype. Our aim was to investigate the influence of these polymorphisms on RA susceptibility and disease activity at the time of diagnosis and after six months of treatment.
Methods: A group of 128 RA patients treated with methotrexate and 122 healthy controls were genotyped for NLRP3 rs35829419 (p. Q705K) and CARD8 rs2043211 (p. C10X) polymorphisms.
Results: RA susceptibility was not influenced by the investigated polymorphisms or their interaction. The investigated polymorphisms explained 8% of variability in DAS28 at the time of diagnosis. Carriers of NLRP3 rs35829419 or CARD8 rs2043211 polymorphisms had significantly higher DAS28 at the time of diagnosis (p=0.003; p=0.022; respectively). Polymorphic CARD8 rs2043211 TT genotype was also associated with higher DAS28 after six months of treatment (p=0.033).
Conclusions: Genetic variability of inflammasome components may contribute to higher disease activity at the time of diagnosis and after 6 months of methotrexate treatment in RA patients. Better understanding of the immunological mechanisms behind a more active course of RA may suggest novel treatment approaches in a subset of patients with a proinflammatory phenotype.
Uvod: Aktivacija NLRP3-inflamazoma može pojačati zapaljenske procese u reumatoidnom artritisu (RA). Funkcionalni polimorfizmi u genima koji kodiraju za njegove komponente NLRP3 i CARD8 dovedeni su u vezu sa proinflamatornim fenotipom. Naš cilj bio je da istražimo uticaj ovih polimorfizama na podložnost RA-u i aktivnost bolesti u vreme dijagnoze i posle šest meseci.
Metode: U grupi od 128 obolelih od RA-a koji su lečeni metotreksatom kao i kod 122 zdravih kontrolnih ispitanika urađena je genotipizacija za polimorfizme NLRP3 rs35829419 (p. Q705K) i CARD8 rs2043211 (p. C10X).
Rezultati: Na podložnost RA-u nisu uticali istraživani polimorfizmi niti njihova interakcija. Istraživani polimorfizmi objašnjavaju 8% varijabilnosti u DAS28 u vreme dijagnoze. Nosioci polimorfizama NLRP3 rs35829419 ili CARD8 rs2043211 imali su značajno viši DAS28 u vreme dijagnoze (p=0,003, odnosno p=0,022). Polimorfni genotip CARD8 rs2043211 TT takođe je bio povezan sa višim DAS28 posle šest meseci lečenja (p=0,033).
Zaključak: Genetska varijabilnost komponenti inflamazoma može dovesti do pojačane aktivnosti bolesti u vreme dijagnoze i posle šest meseci lečenja metotreksatom kod obolelih od RA-a. Bolje razumevanje imunoloških mehanizama koji stoje iza aktivnijeg toka RA-a moglo bi ukazati na nove pristupe u lečenju u podskupu pacijenata sa proinflamatornim fenotipom.
Keywords: BIRC5; NLRP3; inflammasome; polymorphism; rheumatoid arthritis.