Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis.
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 machin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4236099?pdf=render |
| _version_ | 1819066176207060992 |
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| author | Jadwiga Bienkowska Norm Allaire Alice Thai Jaya Goyal Tatiana Plavina Ajay Nirula Megan Weaver Charlotte Newman Michelle Petri Evan Beckman Jeffrey L Browning |
| author_facet | Jadwiga Bienkowska Norm Allaire Alice Thai Jaya Goyal Tatiana Plavina Ajay Nirula Megan Weaver Charlotte Newman Michelle Petri Evan Beckman Jeffrey L Browning |
| author_sort | Jadwiga Bienkowska |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T15:58:12Z |
| format | Article |
| id | doaj.art-5aee8698067a47a9b3e3c6ff98a387d3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T15:58:12Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5aee8698067a47a9b3e3c6ff98a387d32022-12-21T18:58:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11254510.1371/journal.pone.0112545Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis.Jadwiga BienkowskaNorm AllaireAlice ThaiJaya GoyalTatiana PlavinaAjay NirulaMegan WeaverCharlotte NewmanMichelle PetriEvan BeckmanJeffrey L BrowningA 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.http://europepmc.org/articles/PMC4236099?pdf=render |
| spellingShingle | Jadwiga Bienkowska Norm Allaire Alice Thai Jaya Goyal Tatiana Plavina Ajay Nirula Megan Weaver Charlotte Newman Michelle Petri Evan Beckman Jeffrey L Browning Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. PLoS ONE |
| title | Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. |
| title_full | Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. |
| title_fullStr | Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. |
| title_full_unstemmed | Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. |
| title_short | Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. |
| title_sort | lymphotoxin light pathway regulates the interferon signature in rheumatoid arthritis |
| url | http://europepmc.org/articles/PMC4236099?pdf=render |
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