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 leuk
ocyte antigen (HLA) class II polymorphism has been associated with a number
of diseases including autoimmune and inflammatory diseases, asthma, and al
lergy, we investigated the possibility that HLA polymorphism contributes to
CF-associated pulmonary inflammation. Among the 98 adult CF patients teste
d, 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 less than or equal to 10(-6), relative risk [RR] = 22, an
d p less than or equal to 5.10(-4), RR = 27, respectively) and in a random
population. No significant difference of these allelic distributions was fo
und according to the CFTR genotype. In the CF patients, the DR7 allele was
significantly associated with an increase In total IgE and with chronic Pse
udomonas aeruginosa colonization (100% of DR7 versus 83% of non-DR7 patient
s being colonized, p < 0.05). Our results suggest that genetic factors know
n to modulate the immune response might contribute to chronic infection wit
h Pseudomonas, increased total IgE, and pulmonary outcome in CF.