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

Peter Gergely, Rudolf Pullmann, Christina Stancato, Laszlo Otvos, Agnes Koncz, Antal Blazsek, Gyula Poor, Kevin E. Brown, Paul E. Phillips, Andras Perl

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 < 0.0001) or RA controls (23/91; P < 0.0001). TTV prevalence in healthy lupus relatives (40/78) was decreased with respect to lupus patients (80/121; P = 0.0184) and increased with respect to unrelated healthy donors (66/199; P = 0.0026). HRES-1/p28 Western blot reactivity was observed in 12/23 TTV PCR-negative donors and 43/58 TTV PCR-positive donors (P < 0.0281). Conclusions: Increased prevalence of TTV and molecular mimicry with HRES-1/p28 may contribute to generation of antinuclear antibodies and pathogenesis of SLE.

Original languageEnglish
Pages (from-to)124-134
Number of pages11
JournalClinical Immunology
Volume116
Issue number2
DOIs
Publication statusPublished - Aug 1 2005

Keywords

  • Endogenous retrovirus
  • HRES-1
  • SLE
  • TT virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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