Protective effect of the KIR2DS1 gene in atopic dermatitis

Atopic dermatitis (AD) is a common skin disease of complex etiology including affected humoral and cellular immune responses. The role of NK cells in development of this disease has been recently postulated, but is still poorly documented. The current study was undertaken to determine the impact of genes for the most polymorphic NK cell receptors, known as killer cell immunoglobulin-like receptors (KIRs), on the development of AD.     

HLA Class I allele frequencies in the Lebanese population

The highly polymorphic Human Leukocyte Antigen system encompasses different loci that have been studied in transplantation as well as diseases and population associated research. This study is the first and largest of its kind to describe the distribution of HLA-A, -B and -C alleles in Lebanon. Respectively, 1994, 1309 and 1163 Lebanese individuals referred for HLA typing and possible bone marrow/kidney donation were tested for HLA-A, HLA-B and HLA-C alleles using the polymerase chain reaction/Sequence specific priming (PCR-SSP) method. Our data were compared to that of several populations with interesting and common findings shared with the Moroccan, Jordanian, Tunisian, Omani, Korean, Chinese, Japanese, Peruan, Bulgarian, Irish, Polish, Spanish, Swiss, American, African and Brazilian populations. The following data concerning the Lebanese population will help future investigators to study the relation of HLA-A, -B and -C alleles with common diseases in Lebanon and will add to the available international literature. This new data will serve as a major reference report in the region.     

Proteasome inhibitor lactacystin augments natural killer cell cytotoxicity of myeloma via downregulation of HLA class I

Modulation of inhibitory and activating natural killer (NK) receptor ligands on tumor cells represents a promising therapeutic approach against cancer, including multiple myeloma (MM). Human leukocyte antigen (HLA) class I molecules, the NK cell inhibitory killer cell immunoglobulin-like receptor (KIR) ligands, are critical determinants of NK cell activity. Proteasome inhibitors have demonstrated significant anti-myeloma activity in MM patients. In this study, we evaluated the effect of proteasome inhibitors on the surface expression of class I in human MM cells. We found that proteasome inhibitors downregulated surface expression of class I in a dose- and time-dependent manner in MM cell line and patient MM cells. No significant changes in the expression of the MHC class I chain-related molecules (MIC) A/B and the UL16-binding proteins (ULBPs) 1–3 were observed. Downregulation of class I by lactacystin (LAC) significantly enhances NK cell-mediated lysis of MM. Furthermore, the downregulation degree of class I was associated with increased susceptibility of myeloma cells to NK cell killing. HLA blocking antibody produced results that were similar to the findings from proteasome inhibitor. Taken together, our data suggest that proteasome inhibitors, possible targeting inhibitory KIR ligand class I on tumor cells, may contribute to the activation of cytolytic effector NK cells in vitro, enhancing their anti-myeloma activity. Our findings provide a rationale for clinical evaluation of proteasome inhibitor, alone or in combination, as a novel approach to immunotherapy of MM.