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

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.