title: Association of the autoimmune disease scleroderma with an immunologic response to cancer.
abstract: Autoimmune diseases are thought to be initiated by exposures to foreign antigens that cross-react with endogenous molecules. Scleroderma is an autoimmune connective tissue disease in which patients make antibodies to a limited group of autoantigens, including RPC1, encoded by the POLR3A gene. As patients with scleroderma and antibodies against RPC1 are at increased risk for cancer, we hypothesized that the "foreign" antigens in this autoimmune disease are encoded by somatically mutated genes in the patients' incipient cancers. Studying cancers from scleroderma patients, we found genetic alterations of the POLR3A locus in six of eight patients with antibodies to RPC1 but not in eight patients without antibodies to RPC1. Analyses of peripheral blood lymphocytes and serum suggested that POLR3A mutations triggered cellular immunity and cross-reactive humoral immune responses. These results offer insight into the pathogenesis of scleroderma and provide support for the idea that acquired immunity helps to control naturally occurring cancers.
authors: Ludwig Center, the Howard Hughes Medical Institutions, and the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: Christine G
authors: CG
authors: Joseph
authors: Erika
authors: E
authors: Darrah
authors: Ami A
authors: AA
authors: Shah
authors: Andrew D
authors: AD
authors: Skora
authors: Livia A
authors: LA
authors: Casciola-Rosen
authors: Fredrick M
authors: FM
authors: Wigley
authors: Francesco
authors: F
authors: Boin
authors: Andrea
authors: A
authors: Fava
authors: Chris
authors: C
authors: Thoburn
authors: Isaac
authors: I
authors: Kinde
authors: Yuchen
authors: Y
authors: Jiao
authors: Nickolas
authors: N
authors: Papadopoulos
authors: Kenneth W
authors: KW
authors: Kinzler
authors: Bert
authors: B
authors: Vogelstein
authors: Antony
authors: A
authors: Rosen
mesh_terms: D000483:Alleles; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000150:complications* / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D056426:Genetic Loci; D006801:Humans; D020125:Mutation, Missense; D009369:Neoplasms / Q000150:complications / Q000235:genetics / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D012320:RNA Polymerase III / Q000235:genetics / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000150:complications* / Q000235:genetics
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C585825:POLR3A protein, human; D012320:RNA Polymerase III