An antibody deficiency syndrome: Selective immunoglobulin deficiency with reduced synthesis of γ and α immunoglobulin polypeptide chains

Abstract

Selective immunoglobulin deficiencies were identified in a fifteen year old Navajo Indian girl who had had repeated infections from infancy and retarded physical development. The gamma globulins appeared to be normal on paper electrophoresis but immunoelectrophoresis revealed marked immunoglobulin abnormalities. The immunoglobulin abnormalities in this patient were marked reduction in the IgG (7Sγ 2-globulins) and IgA ( β 2 A -globulins), both less than one one-hundredth of normal; and increased IgM ( γ 1-macroglobulins) and IgD, both ten to fifteen times greater than normal. The macroglobulins in this patient appeared to be normal in physiocochemical and immunochemical properties except for the low antibody content. Immune response was impaired, but not completely abolished. There were no cellular deficiencies or abnormalities in either the bone marrow or lymph nodes by routine staining technic. Well developed plasma cells were present in normal or increased numbers. Mature typical plasma cells and lymphoid-plasma cells demonstrated fluorescence with specific anti-IgM, anti-type K (I) and anti-type L (II) antiserums. The evidence presented shows that this patient had a defect in the synthesis of the γ and α heavy polypeptide chains of the immunoglobulins (i.e., those normally present in IgG and IgA molecules). However, synthesis of μ and δ heavy chains (of IgM and IgD molecules) was increased. Synthesis of κ and λ light chains (types I and II) probably was normal. The defective synthesis of γ and α heavy polypeptide chains in this patient is compared with agammaglobulinemia and other selective immunoglobulin deficiency states. The structural genes for the γ and α polypeptide chains were present in this patient. Evidence is presented indicating that defects in the controller or regulatory genes are a major feature of this disorder.