Activation of human complement by mouse and mouse/human chimeric monoclonal antibodies

The complement (C)-activating capabilities in human serum of 32 mouse and 10 mouse/human chimeric MoAbs of different isotypes, and their fragments, were tested in vitro. Activation of C via the classical pathway (CP) was performed in 1% factor D-deficient serum in gelatin containing Veronal buffer in the presence of calcium and magnesium (GVB⁺⁺), while activation of the alternative pathway of C (AP) was assessed in 10% Clq-depleted serum in the presence of 5 mm MgCl₂ in GVB⁺⁺. The C-activating ability of MoAbs was expressed relative to the degree of activation of complement by aggregated IgG for the CP and relative to mouse IgG 1 for the AP. All of seven mouse IgG2a MoAbs were potent activators of the CP. The results of CP activation by IgG1, IgG2b and IgG3 isotypes were different for individual MoAbs. Only three (two IgG 1 and one IgG3) of 32 mouse MoAbs were potent activators of the AP. IgG2a and IgG2b were relatively poor AP activators. There were a few MoAbs which activated both the AP and CP. Of 10 chimeric MoAbs, two IgG1, one IgG2 and one IgG4 were poor or non-activators of the CP. On the other hand, IgG2 and IgG4 were good AP activators. IgG3 was the most potent AP activator. Most of the F(ab')₂ fragments were activators of the AP and displayed no activation of the CP. Fc fragments only activated the CP. whereas Fab'did not activate the CP or the AP. These studies suggest that the route of complement activation by class and subclass MoAbs can not always be predicted in advance and based only on their subclass identity.     

Use of an antibody-ricin A-chain conjugate to delete neoplastic B cells from human bone marrow

Affinity-purified rabbit antibody to human lambda and kappa chains (R alpha H lambda kappa) was conjugated to the A-chain of the plant toxin, ricin. The resulting immunotoxin (R alpha H lambda kappa-A) killed cells from the tumor cell line Daudi, which bears surface immunoglobulin, but was nontoxic to the CFU-E, BFU-E, and CFU-GM of human bone marrow. R alpha H lambda kappa-A eliminated 99% of clonogenic Daudi cells that had been mixed with marrow cells in vitro, without demonstrable toxicity to hematopoietic cells. Thus, in vitro treatment of marrow with R alpha H lambda kappa-A may increase the incidence of cure following autologous bone marrow transplantation for the treatment of human B-cell malignancies.     

HIV infection: increase in public awareness and anxiety.

Between the end of September and mid-November 1986 the number of patients who requested antibody testing for human immunodeficiency virus (HIV) at this department increased by over 300%. This increase followed a media campaign that emphasised the potential heterosexual spread of HIV. After pretest counselling roughly one quarter of the women and of the heterosexual men decided not to be tested. The reason given most often by women for testing was previous sexual intercourse with bisexual or possibly bisexual men. Heterosexual men were most often concerned about previous casual encounters or contact with prostitutes. Of the 641 tests for HIV antibody performed during the last three months of 1986, 37 (5-8%) were positive. Because an increasing number of patients are attending sexually transmitted diseases clinics for HIV antibody testing staffing levels in these clinics need to be reappraised now.