Endogenous and recombinant type I interferons and disease activity in multiple sclerosis

• Published in: PloS one Vol. 7; no. 6; p. e35927
• Main Authors: Sellebjerg, Finn, Krakauer, Martin, Limborg, Signe, Hesse, Dan, Lund, Henrik, Langkilde, Annika, Søndergaard, Helle Bach, Sørensen, Per Soelberg
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.06.2012; Public Library of Science (PLoS)
• Subjects: Adult; Antigens, CD - immunology; Autoimmune diseases; Biological response modifiers; Biology; Care and treatment; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD49d antigen; Chemokines; Cytometry; Dendritic Cells; Denmark; Diagnostic imaging; Disease control; Female; Flow Cytometry; Gene expression; Health risks; Helper cells; Histocompatibility antigen HLA; HLA-DR Antigens - immunology; Humans; Immunoglobulins; Immunotherapy - methods; Integrin alpha4 - immunology; Interferon; Interferon Type I - immunology; Interferon-beta - immunology; Interferon-beta - therapeutic use; Lymphocytes; Lymphocytes T; Magnetic induction; Magnetic resonance; Magnetic Resonance Imaging; Male; Medical treatment; Medicine; Middle Aged; Monocytes; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Neurology; NMR; Nuclear magnetic resonance; Pathogenesis; Patients; Receptors, Transferrin - immunology; Recombinant Proteins - immunology; Statistics, Nonparametric; T cells; T-Lymphocyte Subsets - immunology; Therapy; VLA-4 antigen; Denmark
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035927

Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26(high) T cells, and the percentage of CD4+CD26(high) T cells that were CD49d(high) correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.