Association of altered folylpolyglutamate synthetase pre-mRNA splicing with methotrexate unresponsiveness in early rheumatoid arthritis.

ABSTRACT:

Objectives

An efficient pharmacological response to MTX treatment in RA patients relies on the retention and accumulation of intracellular MTX-polyglutamates catalysed by the enzyme folylpolyglutamate synthetase (FPGS). We recently identified a partial retention of FPGS intron 8 (8PR) as a prominent splice variant conferring FPGS dysfunction and decreased MTX polyglutamylation in acute lymphoblastic leukaemia. Here, we explored the association between FPGS 8PR levels and lack of MTX responsiveness in RA patients.

Methods

Thirty-six patients undergoing MTX treatment were enrolled from the Combinatie behandeling Reumatoide Artritis (COBRA)-light trial. RNA was isolated from blood samples at baseline, 13 weeks and 26 weeks of therapy, from patients in either COBRA-light (n = 21

SUBMITTER: Muller IB 

PROVIDER: S-EPMC7937028 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature