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

Arthritis Rheum. 1995 Nov;38(11):1660-71. doi: 10.1002/art.1780381119.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Antibodies, Antinuclear / immunology
  • Antigens, Nuclear*
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Autoimmune Diseases / immunology*
  • Blotting, Western
  • Cross Reactions
  • HLA-DQ Antigens / genetics
  • HLA-DR Antigens / genetics
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Lupus Erythematosus, Systemic / immunology*
  • RNA, Small Cytoplasmic*
  • Retroviridae Proteins / immunology*
  • Rheumatic Diseases / immunology*
  • Ribonucleoproteins / immunology
  • Ribonucleoproteins, Small Nuclear*
  • snRNP Core Proteins

Substances

  • Antibodies, Antinuclear
  • Antigens, Nuclear
  • Autoantibodies
  • Autoantigens
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • HRES-1 p28 protein, human retroviral element
  • Histocompatibility Antigens Class II
  • RNA, Small Cytoplasmic
  • RO60 protein, human
  • Retroviridae Proteins
  • Ribonucleoproteins
  • Ribonucleoproteins, Small Nuclear
  • SS-A antigen
  • SS-B antigen
  • snRNP Core Proteins