Immunologic compensation in a patient with a large IgH constant region deletion

Background: Deficiencies of serum Ig of the IgG isotype typically predispos e individuals to recurrent infections in some but not all cases, Patients w ith large deletions of the Ig heavy chain genes are free of recurrent and s evere infections, Objective: We sought to determine a mechanism of immunologic compensation t hat would possibly explain the reason for this patient's paucity of infecti on despite lacking several classes of serum Ig, Methods: The patient is a 50-year-old white man, Serum Ig levels and specif ic antibody titers were measured by using various methods, including nephel ometry, enzyme immunoassay, and radial immunodiffusion, The status of the I g heavy chain genes was examined by means of Southern blotting of genomic D NA isolated from EBV-transformed B cells, Results: The patient's serum lacked detectable IgG1, IgG2, IgG4, acid IgA1 levels, Southern blot analysis demonstrated a large heavy chain constant (C ) region gene deletion that included C gamma1, C alpha1, psiC gamma, C gamm a2, and C gamma4. Antibody responses to capsular pneumococcal and hemophilu s polysaccharide antigens were essentially absent, However, IgG3 antibodies against the protein antigen tetanus toroid were present. Relatively high a ntibody titers were found against pneumococcal surface proteins as well, Conclusion: We conclude that our patient's relative freedom From serious in fection may be as a result of production of IgG3 antibodies to pneumococcal capsular proteins.