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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.
- Source :
-
Clinical immunology (Orlando, Fla.) [Clin Immunol] 2005 Aug; Vol. 116 (2), pp. 124-34. - Publication Year :
- 2005
-
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.<br />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.<br />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).<br />Conclusions: Increased prevalence of TTV and molecular mimicry with HRES-1/p28 may contribute to generation of antinuclear antibodies and pathogenesis of SLE.
- Subjects :
- Adult
Amino Acid Sequence
Antibodies immunology
Antibody Affinity immunology
Antigens, Nuclear genetics
Autoantigens genetics
Circoviridae Infections epidemiology
Cross Reactions genetics
Cross Reactions immunology
Enzyme-Linked Immunosorbent Assay
Epitope Mapping
Epitopes, B-Lymphocyte genetics
Epitopes, B-Lymphocyte immunology
Female
Humans
Immunodominant Epitopes genetics
Lupus Erythematosus, Systemic blood
Lupus Erythematosus, Systemic virology
Male
Middle Aged
Molecular Sequence Data
Peptide Fragments chemical synthesis
Peptide Fragments chemistry
Peptide Fragments immunology
Prevalence
Retroviridae Proteins genetics
Sequence Homology, Amino Acid
Torque teno virus genetics
Viral Proteins genetics
Viral Proteins immunology
Viremia diagnosis
Viremia epidemiology
Antigens, Nuclear immunology
Autoantigens immunology
Circoviridae Infections immunology
Immunodominant Epitopes immunology
Lupus Erythematosus, Systemic immunology
Retroviridae Proteins immunology
Torque teno virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-6616
- Volume :
- 116
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 15894513
- Full Text :
- https://doi.org/10.1016/j.clim.2005.04.002