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.
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.
Gergely
Peter
P
Section of Rheumatology, Department of Medicine, State University of New York, Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA.
Pullmann
Rudolf
R
Stancato
Christina
C
Otvos
Laszlo
L
Koncz
Agnes
A
Blazsek
Antal
A
Poor
Gyula
G
Brown
Kevin E
KE
Phillips
Paul E
PE
Perl
Andras
A
D000328:Adult; D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D034961:Antigens, Nuclear / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D018173:Circoviridae Infections / Q000453:epidemiology / Q000276:immunology*; D003429:Cross Reactions / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D015995:Prevalence; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D022783:Torque teno virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014766:Viremia / Q000175:diagnosis / Q000453:epidemiology
D000906:Antibodies; D034961:Antigens, Nuclear; D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; C096557:HRES-1 p28 protein, human retroviral element; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D012191:Retroviridae Proteins; D014764:Viral Proteins