A preliminary assessment of alpha-1 antitrypsin S and Z deficiency allele frequencies in common variable immunodeficiency patients with and without bronchiectasis

Clin Exp Immunol. 2002 Dec;130(3):489-94. doi: 10.1046/j.1365-2249.2002.01995.x.


Common variable immunodeficiency (CVID) is the name given to a clinically heterogeneous group of hypogammaglobulinaemic immunodeficiency states. Bronchiectasis is a feature of this disease and is believed to be the result of recurrent bacterial infection affecting the respiratory tract. Bronchiectasis is also a feature associated with emphysematous changes of the lung in alpha-1 antitrypsin (AAT) deficiency, a serious and relatively common disease, affecting 1 : 2000 in the United Kingdom. This has been demonstrated to result from possession of deficiency alleles, the most clinically important alleles being PI*Z and PI*S. Isolated reports of families with antibody deficiency and AAT deficiency have been published but to date no study has been performed to specifically investigate if AAT deficiency is associated with the lung damage seen in CVID patients. We have developed a PCR genotyping assay that identifies S and Z deficiency alleles and we have used this assay in a preliminary study to investigate the occurrence of these deficiency alleles of AAT in 43 CVID patients. Results of this preliminary study suggest that CVID patients did not have an altered distribution of AAT genes when compared to 70 normal controls. Subgrouping of CVID patients into those with and without bronchiectasis demonstrated a Z allele frequency of 0.077 in those patients with bronchiectasis, which is higher than found in normal controls, namely 0.029 (P < 0.15). Due to the relatively small numbers studied, these results are inconclusive in determining whether AAT deficiency may exacerbate lung damage in some CVID patient, the data does however, indicate that a larger multi-centre study involving many more CVID patients may be useful.

MeSH terms

  • Adult
  • Aged
  • Alleles*
  • Bronchiectasis / genetics
  • Case-Control Studies
  • Chi-Square Distribution
  • Common Variable Immunodeficiency / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Middle Aged
  • Phenotype
  • alpha 1-Antitrypsin / genetics*


  • alpha 1-Antitrypsin
  • alpha 1-antitrypsin, S variant