Studies with human leukocyte lysosomes. Evidence for antilysosome antibodies in lupus erythematosus and for the presence of lysosomal antigen in inflammatory diseases.

Abstract

Human lysosomes were isolated from normal peripheral blood leukoyctes and characterized by electron microscopy, enzyme analysis, and assays for DNA and RNA. Stored sera from 37 unselected patients with systemic lupus erythematosus (SLE), including active and inactive, treated and untreated cases, were tested in complement fixation (CF) reactions with these lysosome preparations. 23 SLE sera exhibited positive CR reactions, as did sera from two patients with "lupoid" hepatitis. The seven SLE sera with strongest CF reactivity also demonstrated gel precipitin reactions with lysosomes. Neither CF nor precipitin reactions with lysosomes were observed with normal sera or with sera of patients with drug-induced lupus syndrome, rheumatoid arthritis (RA), polymyositis, or autoimmune hemolytic anemia. By several criteria the antilysosome CF and precipitin reactions of SLE sera cound not be attributed to antibody to DNA, RNA, or other intracellular organelles. The lysosomal component reactive with SLE sera in CF assays was sedimentable at high speed and is presumably membrane associated. The CF activity of two representative SLE sera was associated with IgG globulins by Sephadex filtration. A search for lysosomal antigen in SLE and related disorders was also made. By employing rabbit antiserum to human lysosomes in immunodiffusion, a soluble lysosomal component, apparently distinct from the sedimentable (membrane-associated) antigen described above, was identified in serum, synovial fluid, or pleural fluid from patients with SLE, RA, ankylosing spondylitis, and leukemoid reaction. An antigenically identical soluble component reactive with the rabbit antiserum could be released in vitro from intact lysosomes by repeated freeze-thaw cycles..