Biomedical subjects
Publications and source records attributed to K A Efetov.
Affinity of IgG to the first complement factor C1q was found out to increase in 10-30% glycol solutions. Analytical ultracentrifugation and turbidity data showed that IgG molecules do not aggregate at such concentrations of glycol. The complement-binding effect may be caused by a conformational transition in the IgG molecules.
The hydrophilic head of melittin (peptide from bee venom) has the amino acid sequence which is very close to the amino acid sequence of C1q-binding site of the IgG molecule. It was shown, that melittin caused the multiple growth of the interaction of C1q with IgG monoclonal antibody. We assume, that the appearance of melittin in blood causes the spontaneous antigen-independent aggregation of IgG and C1q with the following triggering of the classical pathway of the complement cascade and origin of C3a and C5a components. This can be one of the mechanisms of anaphylaxis as an answer to bee venom.
New data concerning biological properties of polyreactive immunoglobulins (PRIG) were obtained as a result of treatment of mouse serum immunoglobulins by 4 M KSCN and are presented in the paper. In particular, the capacity of PRIG to bind C1q, the subunit of the first component of complement was studied. It was shown that PRIG's binding capacity to C1q is similar to that of intact immunoglobulins. Intravenous administration of PRIG into mice together with either sheep red blood cells or heat-inactivated staphylococcal bacteria did not affect the immune response to these antigens. Meanwhile, the same administration of PRIG together with the purified protein derivate of tuberculin resulted in 10-fold increase of mouse antibody response to PPD. These results demonstrate that PRIG can have some immuno-modulating properties concerning low-immunogenic antigens.
As shown by means of temperature-perturbation differential spectrophotometry blood serum immunoglobulins G from patients with gastric cancer and with some other tumors were more resistant to 2 M urea as compared with the immunoglobulins from healthy volunteers and patients with gastric ulcerous disease. The resistance of IgG conformation was altered in the course of gastric cancer treatment.
Influence of urea on the structure of human IgG and isolated Fab and Fc-fragments was investigated by temperature-perturbation difference spectroscopy and circular dichroism. It was shown that 2M urea caused non-denaturational changes of IgG quaternary structure, localized in Fab-fragments. The same changes occur in solutions with ethylene glycol and glycerine as well. Apparently the main cause of these changes is dehydration. It is possible that the investigated effects model the conformational changes which appear in immunoglobulins after antigen binding.
We apply the thermal perturbation difference spectroscopy to demonstrate that immunoglobulins G (IgG) isolated from blood serum of a patient with stomach cancer are more stable to the influence of 12% urea than IgG of a healthy donor. IgG at the same pathology have greater tendency to aggregation than IgG at norm according to the laser correlation spectroscopy data.
Mouse monoclonal IgG1-antibodies (MA) against melittin were used for the investigation of human IgG-C1q binding. The ELISA method, allowing one to determine the dissociation constants of IgG-C1q complex, based on the competition of two IgG (investigating human IgG and MA, labelled by peroxidase) for C1q binding was developed. The method was used to show that IgG in 50% of cases of chronic lymphoid leukemia possessed lesser complement-binding activity than normal human IgG. This effect can be the result of screening of effector centres of immunoglobulins by ligands which appeared in the process of tissue destruction under pathology.
In order to elucidate the mechanism of induction of serum immunoglobulins polyreactive properties by chaotropic ions, gel-chromatography of immunoglobulins in the medium containing 3.3 M KSCN, has been done. It was found that the transformation of serum immunoglobulins to polyreactive antibodies, which could react with different serological unrelated antigens, was not followed by dissociation of any hypothetical blocking factors. Instead, it was demonstrated that the appearance of polyreactive properties of immunoglobulins was likely to depend on conformational changes of immunoglobulin molecules.