Unusual precipitins in pathological human sera.

In conducting double diffusion gel precipitation tests, unexpected, strong precipitation reactions were noticed between a serum originating from a renal graft recipient and many pathological human sera. The highest frequency of positive reactions were produced by sera of patients with infectious mononucleosis (83%), chronic Epstein-Barr virus infections (72%), rheumatoid arthritis (57%), lepromatous leprosy (57%), and AIDS (44%). The precipitin in these pathological sera was identified as an antibody of IgM variety and the precipitinogen in the transplantation serum was shown to be a thermostable component with beta-globulin mobility. No explanation of the nature of reactions observed can be given at present.

Antibodies to Newcastle disease virus in various human diseases.

Sera of patients with infectious mononucleosis (IM) and various other diseases were studied for agglutinins against Newcastle disease virus (NDV)-modified human group O red blood cells (NDVO) and antibodies to the NDV preparations. In agreement with previous studies, the NDVO antibodies are found in a wide variety of diseases in addition to IM, including Japanese IM-like syndrome (22%), syphilis (24%), lepromatous leprosy (30%), systemic lupus erythematosus (29%), multiple sclerosis (18%) and cancer (17%); these antibodies were also found in patients with renal allografts (29%). It was also noted that the Victoria (VIC), Roakin and Herts strains, but not B1 strain of NDV are active in the NDVO agglutination, and VIC and Roakin strains, but not B1 strain in the immunodiffusion. Immunodiffusion and enzyme immunoassay with various preparations of the VIC strain revealed that the major antigen(s) of the virus under study is carried by the hemagglutinin-neuraminidase (H-N) glycoproteins. The H-N molecule was also shown to be able to modify human erythrocytes for the agglutination by the pathologic sera.

Specificity of antibodies to Newcastle disease virus.

Specificity of antibodies to Victoria strain of Newcastle disease virus (NDV) found in infectious mononucleosis (IM) and other pathologic sera was investigated by agglutination of NDV-modified human O red blood cells, as well as by immunodiffusion and enzyme immunoassay with various preparations of the virus. These studies clearly demonstrated that the NDV antibodies are distinct from P-B or H-D antibodies. The unexpected observation that guinea pig kidney (GPK) tissues absorbed NDV antibodies allowed their classification into a group of 'GPK-positive' heterophile antibodies. The simultaneous occurrence of the NDV antibodies and H-D antibodies in IM and other diseases suggests the possibility that multiple new antigenic determinants, especially those of carbohydrate nature, may appear due to the alteration of self-antigens as a result of various pathologic processes.

Studies on the Paul-Bunnell antigen-antibody system. III. Detection of a Paul-Bunnell-related antigen in syphilis and leprosy.

By means of double-diffusion precipitation tests in agarose gel with selected infectious mononucleosis (IM) sera, an antigen was detected in sera of patients with syphilis and leprosy. Of 378 syphilis sera tested 39 (10.3%) and of 36 leprosy sera 7 (19.4%) gave positive results. Sera of patients with various other diseases were negative. This antigen was demonstrable in sera of patients with both early and late syphilis and was shown to be unrelated to cardiolipin. Absorption studies of the IM sera with bovine and sheep erythrocytes and guinea pig tissues revealed that this antigen was identical with or closely related to the previously described B antigen of the Paul-Bunnel (P-B) antigenic complex and distinct from heterophile antigens of Hanganutziu-Deicher (H-D) and of Forssman specificity. However, 2 of 89 syphilis sera without the P-B antigen were shown to contain antigen(s) of H-D specificity. None of the syphilis or the leprosy sera contained P-B antibodies, but H-D antibodies were found in 13% of syphilis sera.

Hanganutziu-Deicher antibodies in infectious mononucleosis and other diseases.

An enzyme immunoassay (EIA) was developed for the detection of heterophile, Hanganutziu-Deicher (H-D) antibodies in sera of patients with infectious mononucleosis (IM) and various other diseases. The EIA with a high m.w. glycoprotein (HMWGP) isolated from bovine erythrocyte stromata was shown to detect H-D antibodies directly, in spite of higher titers of Paul-Bunnell (P-B) antibodies in the IM sera. Absorption and inhibition studies of IM sera demonstrated H-D specificity of the antibodies combining with HMWGP in the EIA. The H-D antibodies were found in sera of 56% Caucasians and 27% of Japanese suffering from IM. The vast majority of the H-D antibodies in IM sera was of IgM class. Sera of patients with various other diseases also gave positive results: rheumatoid arthritis, 22%; syphilis, 19%; cancer of the gastrointestinal tract, 13%; and lepromatous leprosy 9.7%. The incidence of positive results in control sera from apparently healthy subjects was less than 4%. Results of this study confirmed our previous observation that whereas P-B antigens appear in immunogenic form in only IM, the H-D antigen is expressed as an immunogen in various diseases including IM.

Imbalance in T cell subsets in human diseases.

T cell subsets have been evaluated in 232 patients with various immunological diseases and 41 normal individuals used as a control group. An increase in the helper/suppressor ratio (OKT4:OKT8) was often noted in multiple sclerosis (acute attacks and progressive forms), autoimmune hemolytic anemia (without steroids), membranous and IgA-deposit glomerulonephritis, HBs-negative chronic active hepatitis, lepromatous patients with erythema nodosum, and myasthenia gravis. Ratios were usually normal in membranoproliferative nephritis, in lupus erythematosus (at least in steroid treated cases) and in nephrotic syndrome. High values of helper cells have been found in Sezary's syndrome (with low or no suppressor cells) and in mycosis fungoides. Variable data have been obtained in immunodeficiency syndromes. These data have been correlated with age, sex and clinical parameters, as well as with other immunological tests (E rosettes, mitogen responses, mixed lymphocyte reaction, Concanavalin A-induced suppression). From our investigations we have concluded that the study of OKT antibody-defined T cell subsets offers a valuable technique for the further investigation of human immunological diseases.

Hanganutziu-Deicher antigen and antibody in pathologic sera and tissues.

Heterophile, Hanganutziu-Deicher (H-D) antigen was studied in pathologic sera by means of inhibition of agglutination of bovine erythrocytes by H-D antibodies. H-D antigen was demonstrated in 38% of random cancer sera, 25% of lymphoma or leukemia sera, 25% of leprosy sera, 8% of infectious mononucleosis sera, 6% of rheumatoid arthritis sera, and 27% of synovial fluids of rheumatoid arthritis patients. None of 134 normal human sera gave positive results. Some of the inhibition-positive cancer sera formed precipitation lines with H-D antibody-containing sera. Over 50% of various extracts of cancer tissues as well as spleens of lymphoma or leukemia patients were shown to contain H-D antigen by means of the inhibition test.