       Document 0002
 DOCN  M9620002
 TI    Antibody reactivity to the HRES-1 endogenous retroviral element
       identifies a subset of patients with systemic lupus erythematosus and
       overlap syndromes. Correlation with antinuclear antibodies and HLA class
       II alleles.
 DT    9602
 AU    Perl A; Colombo E; Dai H; Agarwal R; Mark KA; Banki K; Poiesz BJ;
       Phillips PE; Hoch SO; Reveille JD; et al; SUNY Health Science Center,
       College of Medicine, Syracuse 13210,; USA.
 SO    Arthritis Rheum. 1995 Nov;38(11):1660-71. Unique Identifier : AIDSLINE
       MED/96062441
 AB    OBJECTIVE. To evaluate the correlation between the presence of
       antibodies to an endogenous retroviral element-encoded nuclear protein
       autoantigen, HRES-1, and the presence of other antinuclear antibodies
       and HLA class II alleles in patients with systemic lupus erythematosus
       (SLE) and overlap syndromes. METHODS. Antibody reactivities to native
       and recombinant proteins and synthetic peptides were assessed by
       counterimmunoelectrophoresis, enzyme-linked immunosorbent assay, and
       Western blotting. HLA class II alleles were determined by
       oligonucleotide typing. RESULTS. Forty-eight percent of the 153 patients
       with autoimmune disease, and 52% of the subgroup with SLE, had HRES-1
       antibodies. In contrast, 3.6% of 111 normal donors, and none of 42
       patients with the acquired immunodeficiency syndrome or 50 asymptomatic
       human immunodeficiency virus 1-infected patients, had HRES-1 antibodies.
       Chi-square analyses revealed a significant association between
       anti-HRES-1 and anti-RNP and an inverse correlation between HRES-1 and
       Ro/La autoantibodies in patients with SLE or overlap syndromes.
       Antigenic epitopes of HRES-1 and the retroviral gag-related region of
       the 70-kd protein component of U1 small nuclear RNP, which share 3
       consecutive highly charged amino acids (Arg-Arg-Glu), an additional Arg,
       and functionally similar Arg/Lys residues, represent cross-reactive
       epitopes between the two proteins. Selective removal of HRES-1
       antibodies from sera of HRES-1-seropositive/RNP-seropositive patients by
       absorption on recombinant HRES-1/glutathione-S-transferase-conjugated
       agarose beads had no effect on anti-RNP reactivities. A comparative
       multivariate analysis of HLA class II genes revealed a differential
       segregation of DQB1 alleles in HRES-1-seropositive versus
       HRES-1-seronegative patients (P = 0.04). While a relative increase of
       DQB1*0402 among HRES-1-seropositive patients was noted across ethnic
       groups (P = 0.02), a decrease of DQB1*0201 and DQB1*0301 was found in
       white HRES-1-seropositive patients (P = 0.04). CONCLUSION.
       Autoantibodies to HRES-1 are detectable in a distinct subset of patients
       with autoimmune disease, primarily in those who do not have antibodies
       to Ro and La. Anti-HRES-1 and anti-RNP reactivities are mediated by
       cross-reactive but separate antibody molecules. HLA-DQB genes, rather
       than HLA-DRB or DQA genes, may have a more significant influence on
       generation of these antinuclear autoantibodies.
 DE    Alleles  Antibodies, Antinuclear/IMMUNOLOGY  Autoantibodies/IMMUNOLOGY
       Autoantigens/IMMUNOLOGY  Autoimmune Diseases/*IMMUNOLOGY  Blotting,
       Western  Comparative Study  Cross Reactions  Histocompatibility Antigens
       Class II/*GENETICS  Human  HLA-DQ Antigens/GENETICS  HLA-DR
       Antigens/GENETICS  Lupus Erythematosus, Systemic/*IMMUNOLOGY
       Retroviridae Proteins/*IMMUNOLOGY  Rheumatic Diseases/*IMMUNOLOGY
       Ribonucleoproteins/IMMUNOLOGY  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

