HLA class II polymorphism in cystic fibrosis. A possible modifier of pulmonary phenotype

Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1464-8. doi: 10.1164/ajrccm.159.5.9807046.


Evolution of lung damage is highly variable in cystic fibrosis (CF) even in patients with the same cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The analysis of genetic factors other than CFTR may help our understanding of genotype-phenotype relationships in CF. As human leukocyte antigen (HLA) class II polymorphism has been associated with a number of diseases including autoimmune and inflammatory diseases, asthma, and allergy, we investigated the possibility that HLA polymorphism contributes to CF-associated pulmonary inflammation. Among the 98 adult CF patients tested, the genotypic frequencies of DR4 and DR7 alleles (serologic group DR53) and DR7/ DQA*0201 haplotype were higher than in 39 selected control subjects without atopy (p </= 10(-)6, relative risk [RR] = 22, and p </= 5.10(-)4, RR = 27, respectively) and in a random population. No significant difference of these allelic distributions was found according to the CFTR genotype. In the CF patients, the DR7 allele was significantly associated with an increase in total IgE and with chronic Pseudomonas aeruginosa colonization (100% of DR7 versus 83% of non-DR7 patients being colonized, p < 0.05). Our results suggest that genetic factors known to modulate the immune response might contribute to chronic infection with Pseudomonas, increased total IgE, and pulmonary outcome in CF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Colony Count, Microbial
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / immunology*
  • Cystic Fibrosis / microbiology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Female
  • Gene Frequency
  • HLA-DQ Antigens / genetics
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Immunoglobulin E / analysis
  • Lung / physiopathology
  • Male
  • Mutation / genetics
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Pseudomonas aeruginosa / isolation & purification


  • CFTR protein, human
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Immunoglobulin E