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.
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.
Authors: Jingxian Zhao; Abeer N Alshukairi; Salim A Baharoon; Waleed A Ahmed; Ahmad A Bokhari; Atef M Nehdi; Laila A Layqah; Mohammed G Alghamdi; Manal M Al Gethamy; Ashraf M Dada; Imran Khalid; Mohamad Boujelal; Sameera M Al Johani; Leatrice Vogel; Kanta Subbarao; Ashutosh Mangalam; Chaorong Wu; Patrick Ten Eyck; Stanley Perlman; Jincun Zhao Journal: Sci Immunol Date: 2017-08-04
Authors: Hong Dang; Deepika Polineni; Rhonda G Pace; Jaclyn R Stonebraker; Harriet Corvol; Garry R Cutting; Mitchell L Drumm; Lisa J Strug; Wanda K O'Neal; Michael R Knowles Journal: PLoS One Date: 2020-11-30 Impact factor: 3.240