title: Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis.
abstract: 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-αβ/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. ClinicalTrials.gov NCT00664716.
authors.affiliation: Translational Medicine, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Bienkowska
authors.affiliation: Translational Medicine, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Norm
authors.initials: N
authors.lastname: Allaire
authors.affiliation: Translational Medicine, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Alice
authors.initials: A
authors.lastname: Thai
authors.affiliation: Translational Medicine, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Jaya
authors.initials: J
authors.lastname: Goyal
authors.affiliation: Translational Medicine, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Plavina
authors.affiliation: Immunobiology, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Ajay
authors.initials: A
authors.lastname: Nirula
authors.affiliation: Global Clinical Operations, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Megan
authors.initials: M
authors.lastname: Weaver
authors.affiliation: Global Clinical Operations, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Newman
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.affiliation: Immunobiology, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Evan
authors.initials: E
authors.lastname: Beckman
authors.affiliation: Immunobiology, Biogen Idec, Cambridge, Massachusetts, United States of America.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Browning
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D007372:Interferons; C000599771:baminercept