Molecular and serologic analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions.
Selective IgG1 deficiency is a rare disease. We report a familial form of IgG1 deficiency, in which IgG1 was undetectable in a 5-yr-old girl with a history of asthma and respiratory tract infections. Her father had an IgG1 level that was one-third of the mean amount found in normal healthy controls. The defect in the proband was caused by a homozygous deletion of the structural gene for C gamma 1. A Southern blot analysis demonstrated that the maternal haplotype contained a deletion encompassing C gamma 1, C psi epsilon 1, C alpha 1, C psi gamma, and C gamma 2, whereas the deletion on the paternal haplotype was confined to the C gamma 1 gene. Neither of these deletions has previously been reported. IgG1 normally constitutes the dominant isotype for antibodies directed against protein Ag, including viral proteins. We have analyzed the immune response to a number of different protein and polysaccharide Ag in the patient and her parents. In the proband, antiviral antibodies were restricted to the IgG3 and IgG4 subclasses. However, the total amount of IgG directed against several viruses was below the concentration found in normal seropositive individuals. The father and the paternal grandfather, both with low serum IgG1 levels, also had asthma, thus indicating a possible causal relationship.
Smith
C I
CI
Department of Clinical Immunology, Karolinska Institute, Huddinge, Sweden.
Hammarström
L
L
Henter
J I
JI
de Lange
G G
GG
D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D002675:Child, Preschool; D002872:Chromosome Deletion; D004406:Dysgammaglobulinemia / Q000097:blood / Q000209:etiology / Q000235:genetics*; D005260:Female; D005803:Genes, Immunoglobulin; D006239:Haplotypes; D006801:Humans; D017099:IgG Deficiency; D007127:Immunoglobulin Constant Regions / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D007143:Immunoglobulin Heavy Chains / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged
D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains