title: Herpesvirus entry mediator-Ig treatment during immunization aggravates rheumatoid arthritis in the collagen-induced arthritis model.
abstract: Previous studies attempting to influence the severity of collagen-induced arthritis (CIA) by modulating the LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator (HVEM) on T cells)/lymphotoxin pathway have yielded conflicting results. To further clarify the role of LIGHT in autoimmune arthritis, a HVEM-Ig fusion protein was used. CIA was induced in DBA1 mice, which were injected i.p. with recombinant HVEM-Ig fusion protein and control Ig at different time points. Severity of clinical arthritis and histologic joint destruction were significantly increased in HVEM-Ig-treated mice compared with control-Ig-treated mice. Collagen II-induced in vitro T cell proliferation and IFN-gamma production was augmented in mice treated with HVEM-Ig, as was the production of IgG2a anti-collagen II Ab. Accordingly, serum concentrations of IFN-gamma and IL-6 were higher in mice treated with HVEM-Ig. In conclusion, HVEM-Ig aggravates autoimmunity in collagen-induced arthritis, which is possibly mediated by interaction with B and T lymphocyte attenuator (BTLA) or CD160, despite the blockade of LIGHT. Hence, HVEM-Ig seems not to be a valid therapeutic option in autoimmune arthritis.
authors.affiliation: Medical Department I, University of Leipzig, Leipzig, Germany. matthias.pierer@medizin.uni-leipzig.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Pierer
authors.forename: Anett
authors.initials: A
authors.lastname: Schulz
authors.forename: Manuela
authors.initials: M
authors.lastname: Rossol
authors.forename: Eva
authors.initials: E
authors.lastname: Kendzia
authors.forename: Diego
authors.initials: D
authors.lastname: Kyburz
authors.forename: Holm
authors.initials: H
authors.lastname: Haentzschel
authors.forename: Christoph
authors.initials: C
authors.lastname: Baerwald
authors.forename: Ulf
authors.initials: U
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000235:genetics; D053259:Lymphotoxin beta Receptor / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D011971:Receptors, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D001323:Autoantibodies; C488868:BTLA protein, mouse; D024043:Collagen Type II; D007141:Immunoglobulin Fc Fragments; D053259:Lymphotoxin beta Receptor; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011993:Recombinant Fusion Proteins; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14