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Le Touquet – Paris-Plage, France

Mathian A.,University Pierre and Marie Curie | Mathian A.,French Institute of Health and Medical Research | Amoura Z.,University Pierre and Marie Curie | Amoura Z.,French Institute of Health and Medical Research | And 8 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives Interferon a (IFNα) plays a central role in the pathogenesis of systemic lupus erythematosus (SLE) and is considered a target for its treatment. In the current study, the ability of active immunisation with a human (hu) IFNα2b Kinoid (IFN-K) to break B cell tolerance to IFNα and to induce huIFNα-neutralising antibodies in mice immunotolerant to huIFNα2b was assessed. Methods IFN-K was manufactured by crosslinking huIFNα2b to keyhole limpet haemocyanin (KLH). Transgenic mice expressing huIFNα2b received by intramuscular injection either saline or polymerised huIFNα2b as controls, or IFN-K, emulsified in ISA51vg adjuvant. Results All of the huIFNa2b-expressing mice immunised with IFN-K generated neutralising antibodies against huIFNα2b. In addition, these antibodies neutralised all 13 subtypes of huIFNα. They also neutralised IFNα activity in sera collected from 10 different patients with active SLE. However, the antibodies did not bind to huIFNγ or huIFNβ. Finally, cellular activation assays showed that immunisation with IFN-K did not induce memory T cells reactive to native huIFNα2b, whereas it did induce memory cells reactive to KLH. Conclusion These results show that active immunisation with IFN-K induces polyclonal antibodies that neutralise all subtypes of huIFNa as well as IFNa in sera from patients with SLE by breaking humoral but not cellular tolerance to IFNα. This suggests that immunisation with IFN-K is a promising new therapeutic strategy for the treatment of SLE. Source


Ghazarian L.,Hopital Saint Vincent de Paul Cochin | Diana J.,Hopital Saint Vincent de Paul Cochin | Simoni Y.,Hopital Saint Vincent de Paul Cochin | Beaudoin L.,Hopital Saint Vincent de Paul Cochin | Lehuen A.,Hopital Saint Vincent de Paul Cochin
Cellular and Molecular Life Sciences | Year: 2013

Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells. Even though extensive scientific research has yielded important insights into the immune mechanisms involved in pancreatic β-cell destruction, little is known about the events that trigger the autoimmune process. Recent epidemiological and experimental data suggest that environmental factors are involved in this process. In this review, we discuss the role of viruses as an environmental factor on the development of type 1 diabetes, and the immune mechanisms by which they can trigger or protect against this pathology. © 2012 Springer Basel AG. Source

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