| Addition of an indoleamine-2,3,-dioxygenase inhibitor to B cell depletion therapy blocks autoreactive B cell activation and recurrence of arthritis. | |
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MedLine Citation:
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PMID: 22294267 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Define the role indoleamine-2,3-dioxygenase (IDO) plays in driving pathogenic B cells responses leading to arthritis and determine if inhibitors of the IDO pathway can be used in conjunction with B cell depletion therapy to prevent the re-emergence of autoantibodies and arthritis following reconstitution of the B cell repertoire. METHODS: Immunoglobulin transgenic mice were treated with the IDO inhibitor 1-methyl-tryptophan (1MT) and followed for the extent of autoreactive B cell activation. Arthritic mice (K/BxN) were treated with B cell depletion therapy alone or in combination with 1MT. Mice were followed for the presence of autoantibody secreting cells, inflammatory cytokines, and joint inflammation. RESULTS: 1MT did not affect the initial activation or survival of autoreactive B cells, but did inhibit their ability to differentiate into autoantibody secreting cells. Treatment with anti-CD20 depleted the B cell repertoire and attenuated arthritis symptoms; however, arthritis symptoms rapidly returned as B cells repopulated the repertoire. Administration of 1MT prior to B cell repopulation prevented the production of autoantibodies, inflammatory cytokines, and flare in arthritis symptoms. CONCLUSION: IDO activity is essential for the differentiation of autoreactive B cells into antibody secreting cells, but is not necessary for their initial stages of activation. Addition of 1MT to B cell depletion therapy prevents the differentiation of autoantibody secreting cells and recurrence of autoimmune arthritis following reconstitution of the B cell repertoire. These data suggest that IDO inhibitors could be used in conjunction with B cell depletion as an effective co-therapeutic strategy in the treatment of rheumatoid arthritis. |
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Authors:
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Elizabeth Pigott; Laura Mandik-Nayak |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-31 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-2-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 by the American College of Rheumatology. |
Affiliation:
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The Lankenau Institute for Medical Research, 100 Lancaster Ave. Wynnewood, PA 19096. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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