The U1-snRNP complex: structural properties relating to autoimmune pathogenesis in rheumatic diseases.
The U1 small nuclear ribonucleoprotein particle (snRNP) is a target of autoreactive B cells and T cells in several rheumatic diseases including systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). We propose that inherent structural properties of this autoantigen complex, including common RNA-binding motifs, B and T-cell epitopes, and a unique stimulatory RNA molecule, underlie its susceptibility as a target of the autoimmune response. Immune mechanisms that may contribute to overall U1-snRNP immunogenicity include epitope spreading through B and T-cell interactions, apoptosis-induced modifications, and toll-like receptor (TLR) activation through stimulation by U1-snRNA. We conclude that understanding the interactions between U1-snRNP and the immune system will provide insights into why certain patients develop anti-U1-snRNP autoimmunity, and more importantly how to effectively target therapies against this autoimmune response.
Kattah
Nicole H
NH
Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. nahanick@stanford.edu
Kattah
Michael G
MG
Utz
Paul J
PJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015551:Autoimmunity; D000939:Epitopes; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D011487:Protein Conformation; D012216:Rheumatic Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000737:chemistry / Q000276:immunology*; D013329:Structure-Activity Relationship; D051193:Toll-Like Receptors / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D017412:Ribonucleoprotein, U1 Small Nuclear; D051193:Toll-Like Receptors