Sera of patients with rheumatoid arthritis contain antibodies to recombinant human T-lymphotrophic virus type I/II envelope glycoprotein p21.

A possible retroviral etiology for rheumatoid arthritis (RA) has been raised by results of recent studies. Therefore, we examined sera of patients with RA, including those with coexisting Felty's syndrome or leukemia of large granular lymphocytes, for the presence of antibodies to retroviral proteins of human T-lymphotrophic virus type I and type II (HTLV-I/II). Reactivity to recombinant HTLV-I envelope protein rgp21 alone was the primary pattern observed. Twenty-five percent of RA sera, 28% of Felty's syndrome sera, and 30% of large granular lymphocyte leukemia/RA sera reacted with rgp21, each significantly more than the 8% of normal sera (P less than 0.01). Removing rheumatoid factor did not abolish reactivity with rgp21 in any of six RA sera tested. Immunoreactivity to the authentic viral protein was confirmed by using purified rgp21 that was cleaved by CNBr to remove the bacterial fusion peptide, or by blocking sera with a synthetic peptide corresponding to the fusion peptide. Only one serum, from a patient with RA, showed definite evidence for prior infection with prototypic HTLV-II. These data indicate that 25% of RA sera have IgG antibodies to recombinant HTLV-I envelope protein rgp21, which is highly homologous to envelope protein gp21 of HTLV-II. These findings provide potentially novel clues regarding the pathogenesis of RA.