Restricted immunoglobulin constant heavy G chain genes in primary immunodeficiencies

Clin Immunol. 2008 Aug;128(2):190-8. doi: 10.1016/j.clim.2008.03.520. Epub 2008 May 23.

Abstract

Some primary immunodeficiencies (PIDs) express low serum levels of antibodies. The constant heavy G chain (IGHG) genes, also representing Fc domains of gamma 3, gamma 1 and gamma 2 on chromosome 14q32.3, genotyped by the alternative IgG subclass allotypes, found in four fixed IGHG haplotypes, designating four B cell variants, were identified by a competitive ELISA and double immunodiffusion. IGHG genes were hypothesized to contribute to the development of PIDs. From 235 Caucasian patients, the homozygous IGHG *bf-n/*bf-n diplotype (B*(bf-n)/B*(bf-n) cells) dominated significantly in 43 IgG2 deficiency (OR 6.0), 32 common variable immunodeficiency (OR 4.6) and 22 Ataxia telangiectasia (OR 3.0) and the IGHG*ga-n/*ga-n diplotype (B*(ga-n)/B*(ga-n) cells) dominated in 53 IgG3 deficiency (OR 10.6) and 21 Wiscott-Aldrich syndrome (OR 4.1). 62 IgA deficiency patients were dominated by both diplotypes (OR 2.3 and OR 2.8 respectively). Restricted IGHG genes, restricted IgG allotypes (Fc domains) and restricted B cells are significant in PIDs for diagnosis, treatment and pathogenetic mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / immunology
  • B-Lymphocytes / immunology
  • Child
  • Chromosomes, Human, 13-15 / genetics
  • Common Variable Immunodeficiency / genetics
  • Gene Frequency
  • Genes, Immunoglobulin / genetics
  • Genotype
  • Humans
  • IgA Deficiency / genetics
  • IgA Deficiency / immunology
  • IgG Deficiency / genetics
  • Immunoglobulin Allotypes / genetics
  • Immunoglobulin Constant Regions / genetics
  • Immunoglobulin G / genetics*
  • Immunoglobulin Heavy Chains / genetics*
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Wiskott-Aldrich Syndrome / genetics

Substances

  • Immunoglobulin Allotypes
  • Immunoglobulin Constant Regions
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains