当前位置： SCI文献检索 > ANNALS OF THE RHEUMATIC DISEASES期刊下所有文献 > Breach of autoreactive B cell tolerance by post-translationally modified proteins.

Breach of autoreactive B cell tolerance by post-translationally modified proteins.

Abstract：

OBJECTIVES:Over 50% of patients with rheumatoid arthritis (RA) harbour a variety of anti-modified protein antibodies (AMPA) against different post-translationally modified (PTM) proteins, including anti-carbamylated protein (anti-CarP) antibodies. At present, it is unknown how AMPA are generated and how autoreactive B cell responses against PTM proteins are induced. Here we studied whether PTM foreign antigens can breach B cell tolerance towards PTM self-proteins. METHODS:Serum reactivity towards five carbamylated proteins was determined for 160 patients with RA and 40 healthy individuals. Antibody cross-reactivity was studied by inhibition experiments. Mass spectrometry was performed to identify carbamylated self-proteins in human rheumatic joint tissue. Mice were immunised with carbamylated or non-modified (auto)antigens and analysed for autoantibody responses. RESULTS:We show that anti-CarP antibodies in RA are highly cross-reactive towards multiple carbamylated proteins, including modified self-proteins and modified non-self-proteins. Studies in mice show that anti-CarP antibody responses recognising carbamylated self-proteins are induced by immunisation with carbamylated self-proteins and by immunisation with carbamylated proteins of non-self-origin. Similar to the data observed with sera from patients with RA, the murine anti-CarP antibody response was, both at the monoclonal level and the polyclonal level, highly cross-reactive towards multiple carbamylated proteins, including carbamylated self-proteins. CONCLUSIONS:Self-reactive AMPA responses can be induced by exposure to foreign proteins containing PTM. These data show how autoreactive B cell responses against PTM self-proteins can be induced by exposure to PTM foreign proteins and provide new insights on the breach of autoreactive B cell tolerance.

journal_name

Ann Rheum Dis

journal_title

Annals of the rheumatic diseases

authors

Dekkers JS,Verheul MK,Stoop JN,Liu B,Ioan-Facsinay A,van Veelen PA,de Ru AH,Janssen GMC,Hegen M,Rapecki S,Huizinga TWJ,Trouw LA,Toes REM

doi

10.1136/annrheumdis-2016-210772

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

1449-1457

issue

eissn

0003-4967

issn

1468-2060

pii

annrheumdis-2016-210772

journal_volume

pub_type

杂志文章

在线工具

Breach of autoreactive B cell tolerance by post-translationally modified proteins.