Activating KIR/HLA complexes in classic Kaposi's Sarcoma

We investigated whether particular KIR/HLA receptor/ligand genotypes would be preferentially present in KSHV-infected and uninfected individuals who have or have not developed cKS.KIR/HLA genotypes were analyzed by molecular genotyping in 50 KSHV-infected individuals who did or did not have cKS and in 33 age-and sex-matched KSHV seronegative individuals.There was no association of individual KIR, HLA or receptor ligand combinations with KSHV infection. However, activating KIR and KIR/HLA genotypes were significantly more frequent in cKS cases, specifically KIR3DS1, KIR2DS1, and KIR2DS1 with its HLA-C2 ligand.A nonspecific inflammatory response triggered by activation of NK cells upon KIR-HLA interaction could be associated with the pathogenesis of KS.Classic Kaposi's Sarcoma (cKS) is a rare vascular neoplasm of the skin related to Kaposi's Sarcoma-associated Herpes Virus (KSHV or Human Herpes Virus 8, HHV-8) infection. KSHV plays a prominent role in the progression of cKS from an angio-proliferative disorder to sarcoma, KSHV infection is nevertheless not sufficient to provoke such progression as not all KSHV-infected individuals develop cKS [1]. Natural killer (NK) cells are central components of the innate immune response against viral infections and tumour growth via direct and indirect mechanisms [2]. The modulation of NK activity is a complex and multi factorial phenomenon triggered by the binding of inhibitory or activating killer cell immunoglobulin-like receptors (KIR) to class I human leukocyte antigens (HLA) [3,4]. When HLA molecules bind activating KIR receptors, a potent inflammatory response finalized at NK cell-mediated destruction of target cells, including transformed tumor cells and virus-infected cells, is stimulated [5]. KIR and HLA loci are highly polymorphic and map in distinct human chromosomes (chromosomes 19 and 6, respectively); both KIR and the specific HLA ligands must be present in order to regulate NK cell activity, such that one without