Major differences in specificity among naturally occurring human IgG-subclass anti-IgE autoantibodies.
BACKGROUND
The specificity of naturally occurring IgG-subclass anti-IgE autoantibodies (a-IgE Ab) was studied by ELISA inhibition assay with a highly purified IgE-DES myeloma protein as a solid-phase antigen. Because the IgG isotypes differ in effector functions, detailed specificity studies of IgG subclass anti-IgE antibodies might clarify their putative role.


METHODS
Selected sera containing a high concentration of a single IgG a-IgE Ab subclass were allowed to react with purified immunoglobulins of all five classes including five different IgE myeloma proteins and papain-derived Fab epsilon and Fc epsilon fragments of IgE-DES.


RESULTS
The inhibition results indicated that IgG1, IgG2, and IgG3 a-IgE Ab reacted in a low-affinity reaction with IgE myeloma protein-restricted determinants because only IgE-DES was inhibitory. Moreover, the reacting epitopes were heat resistant (2 hours, 56 degrees C) and localized in the Fab epsilon-DES fragment. In sharp contrast, IgG4 a-IgE Ab reacted with high affinity to all five IgE myeloma proteins involving heat-susceptible epitopes confined to the Fc epsilon fragment.


CONCLUSIONS
It seems that a majority of IgG a-IgE Ab have a specificity for nonisotypic myeloma-restricted determinants whereas IgG4 a-IgE Ab are mainly isotype specific. These findings ought to be taken into account in the consideration of physiologic implications of IgG a-IgE Ab and in the interpretation of previous investigations in which intact IgE myeloma proteins have been used to detect IgG a-IgE Ab.
Magnusson
C G
CG
Department of Clinical Immunology, Karolinska Institute, Stockholm, Sweden.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D009194:Myeloma Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D009194:Myeloma Proteins; D007073:Immunoglobulin E