Lymphotoxin-LIGHT Pathway Regulates the Interferon Signature in Rheumatoid Arthritis

被引：40

作者：

Bienkowska, Jadwiga ^{[1
]}

Allaire, Norm ^{[1
]}

Thai, Alice ^{[1
]}

Goyal, Jaya ^{[1
]}

Plavina, Tatiana ^{[1
]}

Nirula, Ajay ^{[2
]}

Weaver, Megan ^{[3
]}

Newman, Charlotte ^{[3
]}

Petri, Michelle ^{[4
]}

Beckman, Evan ^{[2
]}

Browning, Jeffrey L. ^{[2
]}

机构：

[1] Biogen Idec Inc, Translat Med, Cambridge, MA USA

[2] Biogen Idec Inc, Immunobiol, Cambridge, MA USA

[3] Biogen Idec Inc, Global Clin Operat, Cambridge, MA USA

[4] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

来源：

PLOS ONE | 2014年 / 9卷 / 11期

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; DENDRITIC CELLS; I INTERFERON; PHASE-I; MONOCLONAL-ANTIBODY; IFN RESPONSE; ALPHA-BETA; ACTIVATION; EXPRESSION; MACROPHAGES;

D O I：

10.1371/journal.pone.0112545

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A subset of patients with autoimmune diseases including rheumatoid arthritis (RA) and lupus appear to be exposed continually to interferon (IFN) as evidenced by elevated expression of IFN induced genes in blood cells. In lupus, detection of endogenous chromatin complexes by the innate sensing machinery is the suspected driver for the IFN, but the actual mechanisms remain unknown in all of these diseases. We investigated in two randomized clinical trials the effects on RA patients of baminercept, a lymphotoxin-beta receptor-immunoglobulin fusion protein that blocks the lymphotoxin-alpha beta/LIGHT axis. Administration of baminercept led to a reduced RNA IFN signature in the blood of patients with elevated baseline signatures. Both RA and SLE patients with a high IFN signature were lymphopenic and lymphocyte counts increased following baminercept treatment of RA patients. These data demonstrate a coupling between the lymphotoxin-LIGHT system and IFN production in rheumatoid arthritis. IFN induced retention of lymphocytes within lymphoid tissues is a likely component of the lymphopenia observed in many autoimmune diseases.

引用

页数：11

共 75 条

[1] Optimization of a high-throughput whole blood expression profiling methodology and its application to assess the pharmacodynamics of interferon (IFN) beta-1a or polyethylene glycol-conjugated IFN beta-1a in healthy clinical trial subjects. [J].