title: HLA alleles, IFN-gamma responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis.
abstract: Recurrent respiratory papillomatosis (RRP) remains an immunologic enigma. Human papillomavirus (HPV) types 6 and 11 are the predominant HPV viruses that cause papilloma development. However, it is unclear why only a very small fraction of HPV-exposed individuals develop RRP. We performed high-resolution HLA class I and II genotyping on 70 randomly selected patients (56 Caucasians and 14 African-Americans) with RRP. We report, for the first time, an increased frequency of HLA-DRB1*0102 in Caucasian patients with RRP, suggesting that this allele predisposes individuals to RRP. Additionally, HLA-DRB1*0301, DQB1*0201, and DQB1*0202 alleles were selectively enriched in Caucasians with severe disease, suggesting that these alleles may regulate disease severity. In contrast, HLA-DQB1*0602 was more frequent in controls than in Caucasians with severe disease, suggesting a severity-sparing effect of this allele. Furthermore, both DQB1*0201 and DQB1*0202 were enriched, whereas DQB1*0602 was absent, in African-Americans. Interestingly, HLA-DRB1*0301 and DQB1*0201 correlated with reduced interferon-gamma expression in patients with RRP. Larger studies are needed to identify other class II major histocompatibility complex alleles that may influence disease predisposition, disease severity, or both, especially in African-American patients, to ultimately illuminate the regulatory effects of these alleles in the predisposition and severity of RRP.
authors.affiliation: Division of Allergy and Immunology, North Shore-Long Island Jewish Research Institute, Department of Pediatrics, Long Island Jewish Medical Center, New Hyde Park, New York, USA. bonagura@lij.edu
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Bonagura
authors.forename: Andrea
authors.initials: A
authors.lastname: Vambutas
authors.forename: James A
authors.initials: JA
authors.lastname: DeVoti
authors.forename: David W
authors.initials: DW
authors.lastname: Rosenthal
authors.forename: Bettie M
authors.initials: BM
authors.lastname: Steinberg
authors.forename: Allan L
authors.initials: AL
authors.lastname: Abramson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shikowitz
authors.forename: David W
authors.initials: DW
authors.lastname: Gjertson
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
mesh_terms: D001741:Black or African American / Q000235:genetics; D016172:DNA Fingerprinting; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D010212:Papilloma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D012142:Respiratory Tract Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D044465:White People / Q000235:genetics
chemical_list: C469553:E6 protein, Human papillomavirus type 11; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D009856:Oncogene Proteins, Viral; D007371:Interferon-gamma