Paradoxical Effects of Endoplasmic Reticulum Aminopeptidase 1 Deficiency on HLA-B27 and Its Role as an Epistatic Modifier in Experimental Spondyloarthritis.

ABSTRACT:

Objective

We undertook this study to examine the functional basis for epistasis between endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 in experimental spondyloarthritis (SpA).

Methods

ERAP1-knockout rats were created using genome editing and bred with HLA-B27/human β₂ -microglobulin-transgenic (HLA-B27-Tg) rats and HLA-B7-Tg rats. The effects of ERAP1 deficiency on HLA allotypes were determined using immunoprecipitation and immunoblotting, flow cytometry, allogeneic T cell proliferation assays, and gene expression analyses. Animals were examined for clinical features of disease, and tissue was assessed by histology.

Results

ERAP1 deficiency increased the ratio of folded to unfolded (β₂ m-free) HLA-B27 heavy chains, while having the op

SUBMITTER: Tran TM 

PROVIDER: S-EPMC9892207 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature