Neutralizing anti-IL-1 receptor antagonist autoantibodies induce inflammatory and fibrotic mediators in IgG4-related disease.

ABSTRACT:

Background

IgG4-related disease (IgG4-RD) is a fibroinflammatory condition involving loss of B-cell tolerance and production of autoantibodies. However, the relevant targets and role of these aberrant humoral immune responses are not defined.

Objective

Our aim was to identify novel autoantibodies and autoantigen targets that promote pathogenic responses in IgG4-RD.

Methods

We sequenced plasmablast antibody repertoires in patients with IgG4-RD. Representative mAbs were expressed and their specificities characterized by using cytokine microarrays. The role of anti-IL-1 receptor antagonist (IL-1RA) autoantibodies was investigated by using in vitro assays.

Results

We identified strong reactivity against human IL-1RA by using a clonally expanded plasmablast-derived

SUBMITTER: Jarrell JA 

PROVIDER: S-EPMC8573062 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature