title: Killer Cell Immunoglobulin-Like Receptor Alleles Alter HIV Disease in Children.
abstract: BACKGROUND
  HLA class I molecules are ligands for killer cell immunoglobin like receptors (KIR) that control the antiviral response of natural killer (NK) cells. However, the effects of KIR and HLA (KIR/HLA) alleles on HIV disease of children have not been studied.
  
  
  METHODS
  993 antiretroviral naïve children with symptomatic HIV infection from PACTG protocols P152 and P300 were genotyped for KIR and HLA alleles using the Luminex platform. Linear regression was used to test the association between genotypes and baseline pre-ART HIV RNA, CD4+ lymphocyte count, and cognitive score, adjusting for age, race/ethnicity and study. The interaction between genetic markers and age was investigated. To account for multiple testing the false discovery rate (FDR) was controlled at 0.05.
  
  
  RESULTS
  Children with the KIR2DS4*ALL FULL LENGTH (KIR2DS4*AFL) allele had higher CD4+ lymphocyte counts. Among children ≤2 years of age, the KIR2DS4*AFL was associated with lower plasma HIV RNA and higher cognitive index scores. KIR Cent2DS3/5_1 had lower CD4+ lymphocyte counts in children ≤2 years of age, while the presence of Tel1, Tel2DS4_2, Tel2DS4_4, Tel8, Tel2DS4_6 had higher CD4+ lymphocyte counts in all children. Presence of Cent2, Cent4 and Cent8 was associated with increased HIV RNA load in children ≤2 years. Presence of KIR3DL1+Bw4 was associated with higher CD4+ lymphocyte counts in all children. Among children >2 years old, KIR3DS1+Bw4-80I was associated with higher plasma HIV RNA, and Bw6/Bw6 was associated with lower plasma HIV RNA compared to children with KIR3DS1+Bw4-80I.
  
  
  CONCLUSIONS
  Presented data show for the first time that specific KIR alleles independently or combined with HLA ligands are associated with HIV RNA and CD4+ lymphocyte counts in infected, antiretroviral naive children; and many of these effect estimates appear to be age dependent. These data support a role for specific KIR alleles in HIV pathogenesis in children.
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Kumud K
authors.initials: KK
authors.lastname: Singh
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Qin
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Sean S
authors.initials: SS
authors.lastname: Brummel
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Konstantia
authors.initials: K
authors.lastname: Angelidou
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Rodney N
authors.initials: RN
authors.lastname: Trout
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Terence
authors.initials: T
authors.lastname: Fenton
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, United States of America.|Rady Children's Hospital, San Diego, California, United States of America.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
mesh_terms: D000293:Adolescent; D000483:Alleles; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR