title: Serum concentration of immunoglobulin G-type antibodies against the whole Epstein-Barr nuclear antigen 1 and its aa35-58 or aa398-404 fragments in the sera of patients with systemic lupus erythematosus and multiple sclerosis.
abstract: Several studies suggest that infection by Epstein-Barr virus (EBV) might be one of the environmental factors which facilitates the development of autoimmune disorders in genetically susceptible individuals. Recent data indicate that high anti-Epstein-Barr nuclear antigen 1 (EBNA)-1 immunoglobulin (Ig)G titre is a strong risk factor for multiple sclerosis (MS) in patients both with and without the main genetic predisposing trait, human leucocyte antigen (HLA)-DRB1*15:01. Because no similar studies have been published in systemic lupus erythematosus (SLE) patients, we determined the HLA-DRB1*15:01 carrier state and the serum titres against the whole EBNA-1 and its small fragments aa35-58 and aa398-404 in 301 SLE patients, 135 MS patients and in 345 healthy controls. The carrier state of the HLA-DRB1*15:01 allele was deduced from genotyping of a tagSNP (rs3135388) by applying a Taqman-based assay. The serum concentrations of antibodies to EBNA-1 and its aa35-58 or aa398-404 fragments were determined using a commercial assay (ETI-EBNA-G) and home-made enzyme-linked immunosorbent assays, respectively. The serum concentration of anti-EBNA-1 antibodies was significantly (P < 0·001) higher both in MS and SLE patients than in controls. Similar significant differences were found both in HLA-DRB1*15:01 carriers and non-carriers. Furthermore, titres of antibodies against the aa35-58 EBNA-1 fragment were elevated both in MS and SLE patients. By contrast, the levels of aa398-404 EBNA-1 antibodies were elevated significantly only in the SLE patients. These findings indicate that high anti-EBNA-1 IgG titres are HLA-DRB1*15:01-independent risk factors not only for MS, but also for SLE, while high antibody titres against the aa398-404 fragment are characteristic for SLE.
authors: Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary. csukadorka@gmail.com
authors: D
authors: D
authors: Csuka
authors: D
authors: D
authors: Simon
authors: R
authors: R
authors: Hóbor
authors: K
authors: K
authors: Uray
authors: Z
authors: Z
authors: Prohászka
authors: Z
authors: Z
authors: Bánlaki
authors: P K
authors: PK
authors: Jani
authors: Á
authors: Á
authors: Szilágyi
authors: F
authors: F
authors: Hudecz
authors: K
authors: K
authors: Rajczy
authors: G
authors: G
authors: Beke
authors: A
authors: A
authors: Boros Major
authors: A
authors: A
authors: Tordai
authors: Z
authors: Z
authors: Illés
authors: T
authors: T
authors: Berki
authors: L
authors: L
authors: Czirják
authors: G
authors: G
authors: Füst
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D010446:Peptide Fragments / Q000097:blood* / Q000276:immunology*
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D059811:HLA-DRB1 Chains; D007074:Immunoglobulin G; D010446:Peptide Fragments; C417029:EBV-encoded nuclear antigen 1
references: J Immunol. 2004 Jan 15;172(2):1287-94
references: 14707107
references: JAMA. 2005 May 25;293(20):2496-500
references: 15914750
references: Genes Immun. 2012 Jan;13(1):14-20
references: 21776012
references: J Med Virol. 2003 Jun;70(2):253-7
references: 12696112
references: J Rheumatol. 1995 Oct;22(10):1852-61
references: 8991981
references: Bull NYU Hosp Jt Dis. 2006;64(1-2):45-50
references: 17121489
references: Neurology. 2011 Jun 7;76(23):1989-95
references: 21646624
references: J Clin Invest. 1997 Dec 15;100(12):3019-26
references: 9399948
references: Mult Scler. 2011 Nov;17(11):1295-300
references: 21757537
references: Ann N Y Acad Sci. 2009 Sep;1173:658-63
references: 19758212
references: Tissue Antigens. 2008 Oct;72(4):401-3
references: 18647361
references: J Autoimmun. 2004 Sep;23(2):127-40
references: 15324931
references: J Autoimmun. 1994 Apr;7(2):179-91
references: 7518683
references: Mult Scler. 2008 Sep;14(8):1120-2
references: 18573815
references: Arthritis Rheum. 2006 Jan;54(1):360-8
references: 16385527
references: Neurology. 2004 Jun 22;62(12):2277-82
references: 15210894
references: Mult Scler. 2011 Oct;17(10):1185-93
references: 21685232
references: Lupus. 1998;7(3):183-91
references: 9607642
references: JAMA. 2001 Dec 26;286(24):3083-8
references: 11754673
references: Autoimmunity. 2008 May;41(4):298-328
references: 18432410
references: Neurology. 2010 Apr 27;74(17):1365-71
references: 20375311
references: Arthritis Res Ther. 2004;6(4):R295-302
references: 15225364
references: Hum Immunol. 2003 Apr;64(4):462-8
references: 12651073
references: Arthritis Rheum. 2001 May;44(5):1122-6
references: 11352244
references: Biopolymers. 2009;92(2):110-5
references: 19140161
references: Autoimmun Rev. 2009 Feb;8(4):337-42
references: 19167523
references: J Autoimmun. 2008 Dec;31(4):362-71
references: 18849143
references: Ann Neurol. 2010 Jun;67(6):824-30
references: 20517945
references: Eur J Neurol. 2012 Jun;19(6):842-6
references: 22221650
references: Arch Neurol. 2006 Jun;63(6):839-44
references: 16606758
references: J Neuroimmunol. 2009 Oct 30;215(1-2):102-7
references: 19733917
references: Proc Natl Acad Sci U S A. 1988 Aug;85(15):5409-13
references: 3399498
references: Neurology. 2008 Mar 25;70(13 Pt 2):1113-8
references: 18272866
references: Expert Rev Neurother. 2008 Mar;8(3):331-3
references: 18345964
references: Rheumatol Int. 2012 Jan;32(1):79-83
references: 20661740
references: Mult Scler. 2009 Feb;15(2):153-8
references: 18845656
references: Best Pract Res Clin Rheumatol. 2008 Oct;22(5):883-96
references: 19028369
references: Eur J Microbiol Immunol (Bp). 2011 Dec;1(4):267-78
references: 24516733
references: Lancet Neurol. 2007 Sep;6(9):773-81
references: 17689148
references: Mult Scler. 2012 May;18(5):569-77
references: 22127897
references: Rheumatology (Oxford). 2010 Sep;49(9):1706-12
references: 20488925
references: Ann Neurol. 2006 Mar;59(3):499-503
references: 16502434