MOLECULAR AND SEROLOGIC ANALYSIS OF A FAMILIAL CASE OF IGG2 DEFICIENCY

Ig subclass deficiencies are an extremely heterogeneous set of immunologic disorders. Up to now, Ig heavy chain constant region gene deletions are their only characterized cause, though association with IGHC and/or HLA polymorphism has been reported, and various types of regulation defects have been postulated. However, insufficient comprehensive studies in the literature have so far prevented the collection of the data and formulation of hypotheses. Lack of IgG2 is one of the most common and clinically significant selective deficiencies. Children without IgG2 are often subject to recurrent infections, usually of bacterial origin. This finding has been correlated to the observed restriction of antipolysaccharide antibodies to this subclass. We report the characterization of a familial case of IgG2 deficiency in which three siblings display very low levels of IgG2 (below 0.1 g/l), but only two suffer from significant episodes of recurrent infections. Standard immunological parameters (IgG, IgA, IgE, IgM and complement levels) have been analyzed in all family members, and the subclass-restricted response to particular antigens has been evaluated. We also ascertained the segregation of IGHC and HLA polymorphism, and performed molecular analysis of the IGHG2 gene and its switch region. The data rule out any simple hereditary model for the deficiency, and indicate that IgG2 deficiency either does not result in an increased susceptibility to infections, or, alternatively, that the siblings differ with regard to compensatory defence mechanism. The study of numerous cases at the different levels of analysis here reported, could lead to a better understanding of the molecular, immunologic, and clinical aspects of Ig subclass deficiencies.