Molecular structure and function of autoantigens in systemic sclerosis.
Autoantibodies in systemic sclerosis target a limited set of nuclear proteins, principally those of the nucleolus and RNA transcription complexes. These antibodies have proved helpful in diagnosis of this disease, and have been used extensively as probes of nuclear structure and function. Despite these advances, the events that initially trigger autoantibody production in systemic sclerosis are not yet known. While these ANA are not known to disrupt cellular processes by entering living cells, or to cause tissue injury (in contrast to SLE, where autoantibodies may mediate tissue damage), it seems likely that they do not merely represent epiphenomena of the disease. Rather, it is logical to assume that their origin is in some manner tied to etiology of systemic sclerosis, since they segregate by syndrome within the spectrum of this disease (for example, anti-kinetochore antibodies occur in limited cutaneous disease, and anti-topoisomerase I and anti-RNA polymerase antibodies occur in diffuse disease), and since they are distinct from the ANA found in other connective tissue diseases in their selectivity for the nucleolus and RNA polymerases.
Lee
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Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA.
Craft
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JE
D034961:Antigens, Nuclear; D001324:Autoantigens / Q000276:immunology*; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology; D004265:DNA Helicases; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D012321:DNA-Directed RNA Polymerases / Q000276:immunology; D004722:Endoribonucleases / Q000276:immunology; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; D006801:Humans; D018386:Kinetochores / Q000276:immunology; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000276:immunology; D035463:Pol1 Transcription Initiation Complex Proteins; D012261:Ribonucleoproteins / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology
D034961:Antigens, Nuclear; D001324:Autoantigens; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; C047458:fibrillarin; C063844:transcription factor UBF; D012321:DNA-Directed RNA Polymerases; D004722:Endoribonucleases; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C058330:mitochondrial RNA-processing endoribonuclease; C077044:EXOSC10 protein, human; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D004264:DNA Topoisomerases, Type I