Evidence for the involvement of two different MHC class II regions in susceptibility or protection in allergic bronchopulmonary aspergillosis

Bela Chauhan, Louis Santiago, Patricia S. Hutcheson, Howard J. Schwartz, Edward Spitznagel, Mario Castro, Raymond G. Slavin, Clifford J. Bellone

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116 Scopus citations

Abstract

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a disease with uncertain pathology. Studies have suggested a pathogenic role for T(H)2 cells. Previously, we demonstrated, in a small group of patients, that T(H)2 reactivity to a major Aspergillus fumigatus antigen was restricted by HLA-DR2 or HLA-DR5 alleles. Objectives: We sought to confirm whether susceptibility to ABPA is exclusively associated with HLA-DR locus and to investigate the involvement of HLA-DQ genes in the development of ABPA. Methods: Genomic DNA was extracted from patients with ABPA, patients without ABPA but with positive A fumigatus skin test responses and asthma or cystic fibrosis, and healthy control subjects. HLA-DR and HLA-DQ genes were detected by using low-resolution typing; high-resolution typing was done only on HLA-DR2- and HLA-DR5-positive individuals by using sequence-specific primers (PCR-SSP). Results: A significantly higher frequency of HLA-DR2 was observed in patients with ABPA versus those without ABPA (corrected P < .01) or healthy control subjects (corrected P < .01). Genotype analysis revealed that susceptibility to ABPA is associated with HLA-DR2 alleles DRB1*1503 and DRB1*1501 and, to a lesser extent, with the HLA-DR5 allele DRB1*1104. The presence of DR4 or DR7 alleles in non-DR2/5 patients with ABPA suggests that these alleles may also be contributing factors in this disease. Another striking observation was the significantly high frequency of HLA-DQ2 in patients without ABPA (67.4%) compared with patients with ABPA (20.5%) and normal control subjects (37.7%), suggesting that these alleles may confer protection in the population without ABPA. Conclusion: These genetic studies suggest that HLA-DR molecules DR2, DR5, and possibly DR4 or DR7 contribute to susceptibility while HLA-DQ2 contributes to resistance and that a combination of these genetic elements determines the outcome of ABPA in patients with cystic fibrosis and asthma.

Original languageEnglish
Pages (from-to)723-729
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume106
Issue number4
DOIs
StatePublished - Jan 1 2000

Keywords

  • Alleles
  • Allergic bronchopulmonary aspergillosis
  • Immune response
  • MHC class II
  • Polymorphism
  • Resistance
  • Susceptibility

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    Chauhan, B., Santiago, L., Hutcheson, P. S., Schwartz, H. J., Spitznagel, E., Castro, M., Slavin, R. G., & Bellone, C. J. (2000). Evidence for the involvement of two different MHC class II regions in susceptibility or protection in allergic bronchopulmonary aspergillosis. Journal of Allergy and Clinical Immunology, 106(4), 723-729. https://doi.org/10.1067/mai.2000.109913