Quantitative determination of retrovirus-specific immune complexes.

ELISA methodology was adapted to measure antigen-specific immune complexes (ASIC) containing retroviral antigens. Using ICs artificially generated from MuLV gp70 and monoclonal antibodies against gp70 we showed that ICs can be quantified by measuring the levels of antibody and antigen and comparing these to the total content of ICs. Furthermore, this method permits determination of the composition of ICs containing an excess of antigen or antibody (i.e., small or large complexes). The levels of the ASIC were correlated with the levels of ICs containing undefined antigen components as determined by the C1q ELISA. Using this method it was possible to determine levels of MuLV gp70 specific ICs in various mouse sera.

Antigens and circulating immune complexes related to the primate retroviral glycoprotein SiSV gp70: prevalence and distribution in human sera.

We have shown previously that antigens and also circulating immune complexes related to the primate retroviral envelope glycoprotein SiSV gp70 correlate with early mortality and survival of 56 patients with acute leukemias and chronic myelogenous leukemia in blast crisis. The prevalence and general distribution of these antigens and immune complexes in human sera was therefore of obvious interest. We now report an analysis of a total of 200 sera from 166 patients. Of these 113 sera were obtained from 84 patients with acute or chronic leukemias and 87 from 82 non-leukemic subjects, including laboratory workers and patients with non-leukemic neoplasias. Antigens and immune complexes were determined by enzyme-linked immunosorbent assays (ELISA). The anti-SiSV gp70 antiserum used predominantly recognized the protein moieties of the glycoproteins. The distribution of SiSV gp70-related antigens and immune complexes was similar among leukemic and non-leukemic sera. The prevalence of SiSV gp70-related antigens was 53% and of SiSV gp70-related immune complexes 49% in all sera. SiSV gp70-related antigens were detected in a somewhat higher proportion of non-leukemic (69%) than leukemic sera (40%), whereas SiSV gp70-related immune complexes and cross-reactive antibodies were more evenly distributed in leukemic and non-leukemic sera (in 46 and 51% of leukemic and 54 and 51% of non-leukemic sera). Presence of antigens correlated with presence of SiSV gp70-related immune complexes in 71% of all sera, but in 13% of all sera antigens were detectable only by determining SiSV gp70-related immune complexes. Total circulating immune complexes did not correlate with SiSV gp70-related immune complexes. The origin and pathophysiological role of the antigens are discussed.

Oncogenic retrovirus from spontaneous murine osteomas. I. Isolation and biological characterization.

Spontaneous osteomas in strain 101 mice, a strain which has a high incidence of benign bone tumours, harbour numerous C-type virus-like particles with pleomorphic characteristics. A cell-free extract from osteomas from two mice induced bone tumours, together with osteopetrosis and lymphomas, in newborn mice of the low incidence NMRI strain after a latent period of 12 to 15 months. When C3H embryo fibroblasts were infected with the osteoma extract, the resulting cell line produced virus (OA MuLVC) with a high titre. OA MuLVC was cloned by serial endpoint dilution and NIH 3T3 cells were productively infected. The resulting virus was named OA MuLVN. OA MuLVC and OA MuLVN also induced bone tumours, osteopetrosis and lymphomas 12 to 15 months after injection into newborn NMRI mice. The isolated virus showed typical characteristics of the murine retrovirus group. Fv-1 host range restriction assays classified the viruses as N-ecotropic and XC-positive. Tryptic p30 peptide analysis and RNase T1 fingerprint analysis of OA MuLVC and OA MuLVN indicated that OA MuLVC contains an Akv-like virus as well as additional components, whereas OA MuLVN is closely related to Akv, but not identical to it. Serological analysis of the envelope proteins using monoclonal antibodies also showed the virus to be similar, but not identical, to Akv virus.

Antigens and circulating immune complexes related to the primate retroviral glycoprotein SiSVgp70. Indicators of early mortality in human acute leukemias and chronic myelogenous leukemias in blast crisis.

Human sera contain antigens and also circulating immune complexes that are related to the primate retroviral envelope glycoprotein gp70 of simian sarcoma/simian sarcoma associated virus (SiSV) and of gibbon ape leukemia virus (GaLV). SiSVgp70 related antigens (AG) and immune complexes (IC) are detected both in leukemic and in nonleukemic sera. In a further analysis of these data, the prognostic significance of SiSVgp70 related AG and IC in leukemic patients was examined. The data show that the presence of SiSVgp70 related AG and IC indicates an unfavorable clinical course and a shorter survival time in acute leukemias (AL) and in chronic myelogenous leukemia in blast crisis (CML-BC). Survival data of 56 of 64 patients tested were analyzed (38 patients with AL and 18 patients with CML-BC). Patients with AL whose sera were positive for SiSVgp70 related AG and IC had a median survival time of 9.5 months after diagnosis versus 16 months for patients negative for such AG and IC. This difference in survival time was more pronounced for patients with acute nonlymphocytic leukemia (ANLL) (6.5 versus 19 months). The difference in survival between SiSVgp70 related AG- and IC-negative and positive groups as tested by life table analysis (log-rank test) is significant (P less than 0.05). Patients with AL of the AG- and/or IC-positive group had fewer complete remissions. Patients who had no remissions belong to the AG- and/or IC-positive group (P = 0.06). Patients with CML-BC whose sera were positive for SiSVgp70 related AG and/or IC had a median survival time of 2 months after diagnosis versus 7 months for patients with sera negative for such AG and IC. As tested by log-rank test, survival curves between the two groups are significantly different (P less than 0.05). These findings suggest that SiSVgp70 related AG and IC may play an important role in the course of acute leukemia and can provide useful prognostic information.