Activating killer cell immunoglobulin-like receptors 3DS1 and 2DS1 protect against developing the severe form of recurrent respiratory papillomatosis.
The polymorphic killer cell immunoglobulin-like receptors (KIR) control natural killer (NK) cell response against viral infection and tumor transformation. Here we investigated if select KIR genes are associated with recurrent respiratory papillomatosis (RRP), a rare disease of the larynx and upper airway caused by human papillomaviruses (HPV)-6/11. DNA from 66 RRP patients and 195 healthy controls were characterized for KIR and HLA gene polymorphism. Patients lacking activating KIR genes 3DS1 and 2DS1 were more common in severe RRP compared with mild-moderate RRP (78.8% vs 48.5%, p = 0.019). Further, patients carrying any of the known susceptible HLA-DRB1/DQB1 alleles were more frequently negative for KIR3DS1 (p = 0.006), KIR2DS1 (p = 0.003) or KIR2DS5 (p = 0.004) compared with controls carrying any of these HLA allotypes. Nearly 80% of the patients with severe disease were missing the protective HLA-DQB1*0602 allele as well as both KIR3DS1 and KIR2DS1 genes. Phenotyping of papilloma-infiltrating mononuclear-cells revealed an elevated numbers of NK cells and CD57(+)CD4(+) T cells in KIR3DS1(-)KIR2DS1(-) patients compared with patients carrying either one or both of these KIRs. Our data suggest that NK cells expressing activating receptors KIR3DS1 and KIR2DS1 may be necessary to trigger an effective early immune response against HPV-infected targets to establish resistance to RRP development.
Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA. bonagura@lij.edu
Vincent R
VR
Bonagura
Zeying
Z
Du
Elham
E
Ashouri
Lihui
L
Luo
Lynda J
LJ
Hatam
James A
JA
DeVoti
David W
DW
Rosenthal
Bettie M
BM
Steinberg
Allan L
AL
Abramson
David W
DW
Gjertson
Elaine F
EF
Reed
Raja
R
Rajalingam
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D052163:Human papillomavirus 6; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000821:virology; D008297:Male; D010212:Papilloma / Q000235:genetics* / Q000276:immunology / Q000821:virology; D030361:Papillomavirus Infections / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D054340:Receptors, KIR / Q000235:genetics*; D054349:Receptors, KIR3DS1 / Q000235:genetics*; D012008:Recurrence; D014412:Tumor Virus Infections / Q000235:genetics* / Q000276:immunology
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C496212:KIR2DS1 protein, human; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1