Epitope spreading: a mechanism for progression of autoimmune disease

• Authors: V.K. Tuohy , P. Kinkel
• Languages of publication: EN

Abstracts

EN

Autoimmune diseases are typically characterized by a persistent inflammatory self-recognition process that ultimately leads to chronic progressive disability. Over the past several years we have addressed the fundamental question of why autoimmune diseases are chronic. Our working hypothesis in these studies has been that autoimmunity involves a continuous acquisition of new self-recognition events, thereby providing an inflammatory steady-state that leads to chronicity. This acquired T cell neoautoreactivity is commonly referred to as epitope spreading. By studying mulitple sclerosis (MS) and its related animal model, experimental autoimmune encephalomyelitis (EAE), we have found that chronic progression of autoimmune disease is invariably linked to the development of any epitope-spreading process that manifests as a cascade of inflammatory T cell neoautoreactivities to a sequential series of predictable new target self-antigens. However, our most recent observations indicated that the emergence of epitope spreading is accompanied by a concurrent regression of the established primary autoreactivity associated with disease onset. Thus, our studies indicate that progression of autoimmune disease involves a shifting of T cell autoreactivity from primary initiating self-determinants to defined cascades of secondary determinants that sustain the inflammatory self-recognition process during progression to chronicity. Our data support the view that the natural development of self-recognition during autoimmune disease may best be understood when considered in the temporal context of an ?epitope du jour? and ?moving target? perspective.

Keywords

EN

AUTOIMMUNITY; DEMYELINATION; MYELIN; T CELL

Discipline

• IMMUNOLOGY: IMMUNOLOGY

• Publisher: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
• Journal: Archivum Immunologiae et Therapiae Experimentalis
• Year: 2000
• Volume: 48
• Issue: 5
• Pages: 347-352

Contributors

author

V.K. Tuohy

author

P. Kinkel

• Document Type: REVIEW
• Publication order reference: V.K. Tuohy, Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA