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

Objective. To evaluate the correlation between the presence of antibod ies to an endogenous retroviral element-encoded nuclear protein autoan tigen, HRES-1, and the presence of other antinuclear antibodies and HL A class II alleles in patients with systemic lupus erythematosus (SLE) and overlap syndromes. Methods. Antibody reactivities to native and r ecombinant proteins and synthetic peptides were assessed by counterimm unoelectrophoresis, enzyme-linked immunosorbent assay, and Western blo tting, HLA class II alleles were determined by oligonucleotide typing. Results. Forty-eight percent of the 153 patients with autoimmune dise ase, and 52% of the subgroup with SLE, had HRES-1 antibodies, In contr ast, 3.6% of 111 normal donors, and none of 42 patients with the acqui red immunodeficiency syndrome or 50 asymptomatic human immunodeficienc y virus 1-infected patients, had HRES-1 antibodies. Chi-square analyse s 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 a nd 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/L ys residues, represent cross-reactive epitopes between the two protein s. Selective removal of HRES-1 antibodies from sera of HRES-1-seroposi tive/RNP-seropositive patients by absorption on recombinant HRES-1/glu tathione-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-se ropositive versus HRES-1-seronegative patients (P = 0.04), While a rel ative increase of DQB10402 among HRES-1-seropositive patients was not ed across ethnic groups (P = 0.02), a decrease of DQB10201 and DQB1*0 301 was found in white HRES-1-seropositive patients (P = 0.04). Conclu sion, Autoantibodies to HRES-1 are detectable in a distinct subset of patients with autoimmune disease, primarily in those who do not have a ntibodies to Ro and La. Anti-HRES-1 and anti-RNP reactivities are medi ated by cross-reactive but separate antibody molecules, HLA-DQB genes, rather than HLA-DRB or DQA genes, may have a more significant influen ce on generation of these antinuclear autoantibodies.