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J Allergy Clin Immunol. 2007 Sep;120(3):570-7. Epub 2007 Jun 11.

HLA-DRB1 alleles control allergic bronchopulmonary aspergillosis-like pulmonary responses in humanized transgenic mice.

Author information

1
Department of Molecular Microbiology and Immunology, Saint Louis University, St Louis, MO, USA.

Abstract

BACKGROUND:

Allergic bronchopulmonary aspergillosis (ABPA) is a lung hypersensitivity disease mediated in part by CD4(+) T(H)2 cells. There is a significant association between ABPA and the HLA-DR2 genotypes DRB1(*)1501 and DRB1(*)1503, whereas resistance might be associated with HLA-DRB1(*)1502.

OBJECTIVE:

We sought to elucidate the role of HLA-DR alleles in allergic inflammation in lungs.

METHODS:

HLA-DR humanized transgenic mice expressing either the susceptible or resistant alleles were analyzed for the nature and extent of pulmonary inflammation after exposure to Aspergillus species antigens.

RESULTS:

Exposed DRB1(*)1501 and DRB1(*)1503 transgenic mice displayed infiltrates made up prominently of eosinophils, which is consistent with the inflammation found in ABPA. The resistant DRB1(*)1502 mice, on the other hand, displayed minimal to moderate inflammation, consisting mainly of T-cell infiltrates. Significantly more mucin was produced in the DRB1(*)1503 and DRB1(*)1501 mice, and their ability to limit the number of Aspergillus species conidia within the lung parenchyma was impaired. Despite their differences, both the DRB1(*)1503 and DRB1(*)1502 strains mounted comparable T cell-proliferative responses to Aspergillus species antigens.

CONCLUSION:

The HLA-DR2 alleles DRB1(*)1501 and DRB1(*)1503 play a major role in the development of allergic pulmonary inflammation. In contrast, the HLA-DR2 allele DRB1(*)1502 mediates a nonallergic T(H)1-like response to the organism, possibly explaining an ABPA resistance factor. These results are in support of our published human studies in patients with cystic fibrosis and asthma.

CLINICAL IMPLICATIONS:

HLA-DR typing in patients with cystic fibrosis and asthma will aid in the identification of individuals at risk for ABPA.

PMID:
17561243
DOI:
10.1016/j.jaci.2007.04.037
[Indexed for MEDLINE]

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