title: Guanine polynucleotides are self-antigens for human natural autoantibodies and are significantly reduced in the human genome.
abstract: In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170,000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.|Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot, Israel.|Department of Nephrology, Rabin Medical Centre, Petach Tikva, Israel.
authors.forename: Ittai
authors.initials: I
authors.lastname: Fattal
authors.affiliation: Department of Computer Science, The Open University of Israel, Raanana, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Shental
authors.affiliation: Bioinformatics and Biological Computing Unit, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shifra
authors.identifier: http://orcid.org/0000-0001-9604-1939
authors.initials: S
authors.lastname: Ben-Dor
authors.affiliation: The Rheumatology Unit, Rabin Medical Centre, Beilinson Hospital, Petach Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Molad
authors.affiliation: Istituto di, Dipartimento di Scienze Cliniche e Molecolari- Clinica Medica, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Gabrielli
authors.affiliation: The Rheumatology Unit, Rabin Medical Centre, Beilinson Hospital, Petach Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Elisheva
authors.initials: E
authors.lastname: Pokroy-Shapira
authors.affiliation: The Rheumatology Unit, Rabin Medical Centre, Beilinson Hospital, Petach Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shirly
authors.initials: S
authors.lastname: Oren
authors.affiliation: Department of Medicine F, Sheba Medical Centre, Tel Hashomer, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
authors.affiliation: The Rheumatology Unit, Sheba Medical Centre, Tel Hashomer, Israel.
authors.forename: Pnina
authors.initials: P
authors.lastname: Langevitz
authors.affiliation: Department of Medicine C, Wolfson Medical Centre, Holon, Israel.
authors.forename: Gisele
authors.initials: G
authors.lastname: Zandman-Goddard
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Sarig
authors.affiliation: Science in Action Ltd, Weizmann Science Park, Ness-Ziona, Israel.
authors.forename: Raanan
authors.initials: R
authors.lastname: Margalit
authors.affiliation: Department of Nephrology, Rabin Medical Centre, Petach Tikva, Israel.
authors.forename: Uzi
authors.initials: U
authors.lastname: Gafter
authors.affiliation: Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eytan
authors.initials: E
authors.lastname: Domany
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Irun R
authors.initials: IR
authors.lastname: Cohen
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D018899:CpG Islands; D004331:Drosophila melanogaster / Q000235:genetics; D005260:Female; D015894:Genome, Human; D049750:Genome, Insect; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010392:Pemphigus / Q000235:genetics / Q000276:immunology; D011068:Poly G / Q000235:genetics* / Q000276:immunology*; D011071:Poly T / Q000235:genetics / Q000276:immunology; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology; D013045:Species Specificity
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011071:Poly T; D011068:Poly G
keywords: antigens/peptides/epitopes; autoantibodies; human