Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2005-08, Vol.116 (2), p.124-134
• Main Authors: Gergely, Peter, Pullmann, Rudolf, Stancato, Christina, Otvos, Laszlo, Koncz, Agnes, Blazsek, Antal, Poor, Gyula, Brown, Kevin E., Phillips, Paul E., Perl, Andras
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Antibodies - immunology; Antibody Affinity - immunology; Antigens, Nuclear - genetics; Antigens, Nuclear - immunology; Autoantigens - genetics; Autoantigens - immunology; Biological and medical sciences; Circoviridae Infections - epidemiology; Circoviridae Infections - immunology; Cross Reactions - genetics; Cross Reactions - immunology; Endogenous retrovirus; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes, B-Lymphocyte - genetics; Epitopes, B-Lymphocyte - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HRES-1; Humans; Immunodominant Epitopes - genetics; Immunodominant Epitopes - immunology; Immunopathology; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - virology; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Peptide Fragments - immunology; Prevalence; Retroviridae Proteins - genetics; Retroviridae Proteins - immunology; Sequence Homology, Amino Acid; SLE; Torque teno virus - genetics; Torque teno virus - immunology; transfusion-transmitted virus; TT virus; Viral Proteins - genetics; Viral Proteins - immunology; Viremia - diagnosis; Viremia - epidemiology
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2005.04.002

Objective: Systemic lupus erythematosus (SLE) patients produce autoantibodies to HRES-1/p28, a human endogenous retrovirus-encoded nuclear protein. To identify cross-reactive viral antigens capable of triggering autoreactivity, HRES-1/p28 epitopes were mapped by SLE antibodies. Methods: Forty-four peptides overlapping HRES-1/p28 and 13 viral peptides were synthesized on cellulose membrane and tested for recognition by antibodies from 16 HRES-1 Western blot seropositive SLE patients. Transfusion-transmitted virus (TTV) was detected by gene amplification in sera of 211 SLE patients, 78 healthy SLE family members, 199 unrelated healthy donors, and 91 rheumatoid arthritis (RA) patients. Results: HRES-1/p28 residues 41–55, 121–135, and 156–170 were recognized by 12/16 (75.0%), 11/16 (68.8%), and 9/16 lupus sera (56.25%) and considered immunodominant. HRES-1/p28 residues 121–135 harbor cross-reactive epitope with retroviral peptides and the 70 K U1snRNP lupus autoantigen. HRES-1/p28 residues 41–55 and 156–170 exhibited the highest prevalence of cross-reactivity with TTV peptide ORF2a (14/16, 87%). Prevalence of TTV DNA was increased in lupus patients (120/211) with respect to healthy (66/199; P