Antigen-Selective Immune Deficiencies
Those are immunodeficiencies in which the affected patients fail to produce antibodies following a challenge with a specific antigen, while exhibiting normal immune responses to most other antigens.
Two basic mechanisms can, at least theoretically, underlie antigen-specific immune defi-ciencies:
“Holes” in the immunoglobulin repertoire of the responding T-cell receptor implying that no binding sites for a given antigen are available either at the T- or at the B-cell level. Considering that immunogenic proteins are complex molecules with a variety of different epitopes, it is difficult to envisage how this mecha-nism could be involved. In the case of polysaccharides, simpler in structure and presenting a limited number of epitopes to the immune system, the hypothesis is more plausible.
Inefficient antigen presentation to helper T cells, implying that the nonresponse is a consequence of the lack of MHC-II molecules with adequate sites for binding of key peptides derived from antigen processing. This mechanism would apply only to T-dependent responses.
Antigen-selective immune deficiencies are often undiagnosed and often asymptomatic. For example, using tetanus toxoid as immunogen, one can detect about 1 in 100 individuals whose humoral response is consistently low or undetectable, and the same is probably true with other immunogens. Patients who suffer from antigen-selective immune deficiencies and who have frequent infections are often misdiagnosed because most of the tests to eval-uate the immune system are normal. In some symptomatic cases, one or more of the IgG subclasses may be deficient. IgG2 deficiency can be associated with infections by polysac-charide-encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus in-fluenzae.
The diagnosis is eased on the failure to demonstrate the production of specific antibody fol-lowing challenge by infection or immunization.
Replacement of antibody deficiency can be achieved with IVIg. Specific humanized mon-oclonal antibodies may be used to treat this disorder in the future
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