Importance Of Killer Immunoglobulin-like Receptors In Allogeneic Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA) compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients) can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.332126130Moretta, A., Marcenaro, E., Parolini, S., Ferlazzo, G., Moretta, L., NK cells at the interface between innate and adaptive immunity (2008) Cell Death Differ, 15 (2), pp. 226-233Andoniou, C.E., Andrews, D.M., Degli-Esposti, M.A., Natural killer cells in viral infection: More than just killers (2006) Immunol Rev, 214, pp. 239-250Gardiner, C.M., Killer cell immunoglobulin-like receptors on NK cells: The how, where and why (2008) Int J Immunogenet, 35 (1), pp. 1-8Rajagopalan, S., Long, E.O., Understanding how combinations of HLA and KIR genes influence disease (2005) J Exp Med, 201 (7), pp. 1025-1029McVicar, D.W., Burshtyn, D.N., Intracellular signaling the killer immunoglobulin-like receptors and Ly49 (2001) Sci STKE, (75). , re1Rajagopalan, S., Long, E.O., A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells (1999) J Exp Med, 189 (7), pp. 1093-1100. , Erratum in: J Exp Med 2000;191(11): following 2027O'Connor, G.M., Hart, O.M., Gardiner, C.M., Putting the natural killer cell in its place (2006) Immunology, 117 (1), pp. 1-10Boyton, R.J., Altmann, D.M., Natural killer cells, killer immunoglobulinlike receptors and human leukocyte antigen class I in disease (2007) Clin Exp Immunol, 149 (1), pp. 1-8Katz, G., Markel, G., Mizrahi, S., Arnon, T.I., Mandelboim, O., Recognition of HLA-Cw4 but not HLA-Cw6 by the NK cell receptor killer cell Ig-like receptor two-domain short tail number 4 (2001) J Immunol, 166 (12), pp. 7260-7267Laguila, V.J.E., Lieber, S.R., Lopes, P.L.B., Dutra, M.S.B., Vigorito, A.C., Penteado, A.F.J., Relationship between cytokine gene polymorphisms and graft-versus-host disease after allogeneic stem cell transplantation in a Brazilian population (2005) Cytokine, 32 (3-4), pp. 171-177Viel, D.O., Tsuneto, L.T., Sossai, C.R., Lieber, S.R., Marques, S.B., Vigorito, A.C., IL2 and TNFA gene polymorphisms and the risk of graft versus host disease after allogeneic stem cell transplantation (2007) Scand J Immunol, 66 (6), pp. 703-710Vizoni, S.L., Lieber, S.R., de Souza, C.A., Sell, A.M., Visentainer, J.E., Papel das citocinas na imunopatogênese da doença do enxerto contra o hospedeiro (2008) Rev Bras Hematol Hemoter, 30 (2), pp. 142-152Koh, L.P., Rizzieri, D.A., Chao, N.J., Allogeneic hematopoietic stem cell transplant using mismatched/haploidentical donors (2007) Biol Blood Marrow Transplant, 13 (11), pp. 1249-1267Kärre, K., Immunology. A perfect mismatch (2002) Science, 295 (5562), pp. 2029-2031. , Comment on: Science. 2002;295(5562):2097-100Science. 2002;295(5562):2094-7Ruggeri, L., Capanni, M., Casucci, M., Volpi, I., Tosti, A., Perruccio, K., Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation (1999) Blood, 94 (1), pp. 333-339Ruggeri, L., Capanni, M., Urbani, E., Perruccio, K., Shlomchik, W.D., Tosti, A., Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants (2002) Science, 295 (5562), pp. 2097-2100. , Comment in: Science. 2002;295 (5562):2029-31Bishara, A., de Santis, D., Witt, C.C., Brautbar, C., Christiansen, F.T., Or, R., The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreative T cells causing GVHD (2004) Tissue Antigens, 63 (3), pp. 204-211Miller, J.S., Soignier, Y., Panoskaltsis-Mortari, A., McNearney, S.A., Yun, G.H., Fautsch, S.K., Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer (2005) Blood, 105 (8), pp. 3051-3057Keller, M.D., Chen, D.F., Condron, S.A., Liu, N., Reinsmoen, N.L., Buckey, R.H., The effect of natural killer cell killer Ig-like receptor alloreactivity on the outcome of bone marrow stem cell transplantation for severe combined immunodeficiency (SCID) (2007) J Clin Immunol, 27 (1), pp. 109-116. , Erratum in: J Clin Immunol. 2007;27(6):659Ruggeri, L., Mancusi, A., Capanni, M., Urbani, E., Carotti, A., Aloisi, T., Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: Challenging its predictive value (2007) Blood, 110 (1), pp. 433-440Ruggeri, L., Aversa, F., Martelli, M.F., Velardi, A., Allogeneic hematopoietic transplantation and natural killer cell recognition of missing self (2006) Immunol Rev, 214, pp. 202-218Cook, M.A., Milligan, D.W., Fegan, C.D., Darbyshire, P.J., Mahendra, P., Craddock, C.F., The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia (2004) Blood, 103 (4), pp. 1521-1526Witt, C.S., Christiansen, F.T., The relevance of natural killer cell human leukocyte antigen epitopes and killer cell immunoglobulinlike receptors in bone marrow transplantation (2006) Vox Sang, 90 (1), pp. 10-20Hsu, K.C., Keever-Taylor, C.A., Wilton, A., Pinto, C., Heller, G., Arkun, K., Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes (2005) Blood, 105 (12), pp. 4878-4884Schellekens, J., Rozemuller, E.H., Petersen, E.J., van den Tweel, J.G., Verdonck, L.F., Tilanus, M.G., Activating KIRs exert a crucial role on relapse and overall survival after HLA-identical sibling transplantation (2008) Mol Immunol, 45 (8), pp. 2255-2261(2011) Registro Nacional De Doadores De Medula Óssea (REDOME), , http://www.inca.gov.br/conteudo_view.asp?ID=677, Instituto Nacional de Câncer, Brasília: INCA, [cited 2011 Jan 12]. Available fromDavies, S.M., Ruggieri, L., Defor, T., Wagner, J.E., Weisdorf, D.J., Miller, J.S., Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants (2002) Blood, 100 (10), pp. 3825-3827Giebel, S., Locatelli, F., Lamparelli, T., Velardi, A., Davies, S., Frumento, G., Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors (2003) Blood, 102 (3), pp. 814-819Bornhauser, M., Schwerdtfeger, R., Martin, H., Frank, K.H., Theuser, C., Ehninger, G., Role of KIR ligand incompatibility in hematopoietic stem cell transplantation using unrelated donors (2004) Blood, 103 (7), pp. 2860-2861. , author reply 2862. Comment on: Blood. 2003102(3):814-9Beelen, D.W., Ottinger, H.D., Ferencik, S., Elmaagacli, A.H., Peceny, R., Trenschel, R., Genotypic inhibitory killer immunoglobulinlike receptor ligand incompatibility enhances the long term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias (2005) Blood, 105 (6), pp. 2594-2600de Santis, D., Bishara, A., Witt, C.S., Nagler, A., Brautbar, C., Slavin, S., Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants (2005) Tissue Antigens, 65 (6), pp. 519-528Hsu, K.C., Gooley, T., Malkki, M., Pinto-Agnello, C., Dupont, B., Bignon, J.D., Bornhäuser, M., Petersdorf, E., International Histocompatibility Working Group. KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy (2006) Biol Blood Marrow Transplant, 12 (8), pp. 828-836Farag, S.S., Bacigalupo, A., Eapen, M., Hurley, C., Dupont, B., Caligiuri, M.A., Boudreau, C., Davies, S.M., KIR Study Group, Center for International Blood and Marrow Transplantation Research. The effect of KIR ligand incompatibility on the outcome of unrelated donor transplantation: A report from the center for international blood and marrow transplant research, the European blood and marrow transplant registry, and Dutch registry (2006) Biol Blood Marrow Transplant, 12 (8), pp. 876-884Giebel, S., Nowak, I., Wojnar, J., Markiewicz, M., Dziaczkowska, J., Wylezol, I., Impact of activating killer immunoglobulin-like receptor genotype on outcome of unrelated donor-hematopoietic cell transplantation (2006) Transplant Proc, 38 (1), pp. 287-291Han, M., Fallena, M., Guo, Y., Stastny, P., Natural killer cell crossmatch: Functional analysis of inhibitory killer immunoglobulin-like receptors and their HLA ligands (2007) Hum Immunol, 68 (6), pp. 507-51

Association Between Human Leukocyte Antigens And Graft-versus-host Disease Occurrence After Allogenic Hematopoietic Stem Cell Transplantation [associação Entre Antígenos Leucocitários Humanos E A Ocorrência Da Doença Do Enxerto Contra O Hospedeiro Após O Transplante Alogênico Decélulas-tronco Hematopoiéticas]

CONTEXT AND OBJECTIVE: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. DESIGN AND SETTING: Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). METHODS: The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. RESULTS: Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1 *15 (P = 0.0211) and DQB1 *05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). CONCLUSION:This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.1304219224Dickinson, A.M., Charron, D., Non-HLA immunogeneticsin hematopoietic stem cell transplantation (2005) Curr Opin Immunol, 17 (5), pp. 517-525Charron, D., Immunogenetics today: HLA, MHC and much more (2005) Curr Opin Immunol, 17 (5), pp. 493-497Mohyeddin Bonab, M., Alimoghaddam, K., Vatandoust, S., Are HLA antigens a risk factor for acute GVHD in thalassemic patients receiving HLA-identical stem cell transplantation? (2004) Transplant Proc, 36 (10), pp. 3190-3193Battiwalla, M., Hahn, T., Radovic, M., Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence (2006) Blood, 107 (5), pp. 1970-1973Storb, R., Prentice, R.L., Hansen, J.A., Thomas, E.D., Association between HLA-B antigens and acute graft-versus-host disease (1983) Lancet, 2 (8354), pp. 816-819Clark, R.E., Hermans, J., Madrigal, A., HLA-A3 increases and HLA-DR1 decreases the risk of acute graft-versus-host disease after HLA-matched sibling bone marrow transplantation for chronic myelogenous leukaemia (2001) BrJ Haematol, 114 (1), pp. 36-41Weisdorf, D., Hakke, R., Blazar, B., Risk factors for acute graft-versus-host disease in histocompatible donor bone marrow transplantation (1991) Transplantation, 51 (6), pp. 1197-1203Bross, D.S., Tutschka, P.J., Farmer, E.R., Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow (1984) Blood, 63 (6), pp. 1265-1270Remberger, M., Persson, U., Hauzenberger, D., Ringdén, O., An association between human leucocyte antigen alleles and acute and chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation (2002) Br J Haematol, 119 (3), pp. 751-759Ghavamzadeh, A., Alimoghaddam, K., Behrouzan, O., HLA and risk of acute graft versus host disease in allogenic bone marrow transplantation from an HLA-identical sibling (2002) Arch Irn Med, 5 (1), pp. 16-20. , http://www.ams.ac.ir/AIM/0251/aim025116.htm, Available from, Accessed in 2011 (Nov 22)Adams, K.M., Holmberg, L.A., Leisenring, W., Risk factors for syngeneic graft-versus-host disease after adult hematopoietic cell transplantation (2004) Blood, 104 (6), pp. 1894-1897Stern, M., Passweg, J., Tiercy, J.M., Human leukocyte antigen DR15 is associated with reduced relapse rate and improved survival after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation (2006) Biol Blood Marrow Transplant, 12 (11), pp. 1169-1175Petersdorf, E.W., Malkki, M., Genetics of risk factors for graft-versus-host disease (2006) Semin Hematol, 43 (1), pp. 11-23Glucksberg, H., Storb, R., Fefer, A., Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors (1974) Transplantation, 18 (4), pp. 295-304Atkinson, K., Horowitz, M.M., Gale, R.P., Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease (1989) Bone Marrow Transplant, 4 (3), pp. 247-254. , Committee of the International Bone Marrow Transplant RegistryVisentainer, J.E., Lieber, S.R., Persoli, L.B., Serum cytokine levels and acute graft-versus-host disease after HLA-identical hematopoietic stem cell transplantation (2003) Exp Hematol, 31 (11), pp. 1044-1050Vigorito, A.C., Azevedo, W.M., Marques, J.F., A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies (1998) Bone Marrow Transplant, 22 (12), pp. 1145-1151Lin, M.T., Storer, B., Martin, P.J., Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation (2003) N Engl J Med, 349 (23), pp. 2201-2210Laguila Visentainer, J.E., Lieber, S.R., Lopes Persoli, L.B., Relationship between cytokine gene polymorphisms and graft-versus-host disease after allogeneic stem cell transplantation in a Brazilian population (2005) Cytokine, 32 (3-4), pp. 171-177Hsu, K.C., Keever-Taylor, C.A., Wilton, A., Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes (2005) Blood, 105 (12), pp. 4878-4884Viel, D.O., Tsuneto, L.T., Sossai, C.R., IL2 andTNFA gene polymorphisms and the risk of graft-versus-host disease after allogeneic haematopoietic stem cell transplantation (2007) Scand J Immunol, 66 (6), pp. 703-710Azarpira, N., Ramzi, M., Aghdaie, M.H., Darai, M., Geramizadeh, B., Interleukin-10 gene polymorphism in bone marrow transplant recipients (2008) Exp Clin Transplant, 6 (1), pp. 74-79Schellekens, J., Rozemuller, E.H., Petersen, E.J., Activating KIRs exert a crucial role on relapse and overall survival after HLA-identical sibling transplantation (2008) Mol Immunol, 45 (8), pp. 2255-2261Visentainer, J.E.L., Sell, A.M., Franceschi, D.A., Lieber, S.R., Souza, C.A., Importância de polimorfismos de genes reguladores de citocinas em transplantes de células progenitoras hematopoiéticas [Importance of regulatory cytokine gene polymorphisms in hematopoietic stem cell transplantation] (2008) RBCF Rev Bras Ciênc Farm (Impr), 44 (4), pp. 739-74

Influence Of Kir Genes And Their Hla Ligands In Susceptibility To Dengue In A Population From Southern Brazil

Killer cell immunoglobulin-like receptors (KIR) form a group of regulatory molecules that specifically recognise human leukocyte antigen (HLA) class I molecules, modulating the cytolytic activity of natural killer cells. The purpose of this study was to investigate the influence of KIR genes and their class I HLA ligands in susceptibility to dengue fever in a population from southern Brazil through a case-control study. One hundred four subjects with confirmed diagnoses of dengue participated in this study, along with a control group of 172 individuals from the same geographic area. HLA and KIR genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP) and with sequence-specific primer (PCR-SSP) techniques, respectively. Data analysis showed significant differences for the KIR2DS1 (54.8% vs 40.7%, P=0.03), KIR2DS5 (50.0% vs 36.0%, P=0.03) and KIR2DL5 (76.0% vs 56.4%, P=0.001) genes. With regard to KIR-ligand pairs, positive associations with dengue were observed in KIR3DS1-Bw4 (45.2% vs 29.7%, P=0.01), KIR3DL1-Bw4 (80.7% vs 65.1%, P<0.001), KIR2DL1-C2 (75.0% vs 62.2%, P=0.03) and KIR2DS1-C2 (40.4% vs 25.6%, P=0.01) interactions, and a negative association in KIR2DL3-C1/C1 (18.2% vs 33.1%, P = 0.01). Furthermore, the analysis of KIR haplogroups showed a possible protective factor against dengue fever in individuals with the AA genotype. Taken together, these results suggest the existence of genetic predisposition to dengue fever in the population from southern Brazil. © 2013 John Wiley & Sons A/S.826397404Guzman, M.G., Kouri, G., Dengue and dengue hemorrhagic fever in the Americas: lessons and challenges (2003) J Clin Virol, 27, pp. 1-13(2012) Dengue and Severe Dengue, , http://www.who.int/mediacentre/factsheets/fs117/en/, WHO. Geneva: World Health Organization, Available at:Martina, B.E., Koraka, P., Osterhaus, A.D., Dengue virus pathogenesis: an integrated view (2009) Clin Microbiol Rev, 22, pp. 564-581Halstead, S.B., Observations related to pathogenesis of dengue hemorrhagic fever (1970) Yale J Biol Med, 42, pp. 350-360Rosen, L., La pathogenèse de la dengue hemorragique: discussion critique des hypothèses Actuelles (1986) Bull Soc Pathol, 79, pp. 342-349Whitehorn, J., Farrar, J., Dengue (2010) Br Med Bull, 95, pp. 161-173Pelak, K., Need, A.C., Fellay, J., Copy number variation of KIR genes influences HIV-1 control (2011) PLoS Biol, 9, pp. e1001208Alter, G., Martin, M.P., Teigen, N., Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes (2007) J Exp Med, 204, pp. 3027-3036Marangon, A.V., Silva, G.F., Verdichio de Moraes, C.F., KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C (2011) Hum Immunol, 72, pp. 1074-1078Rauch, A., Laird, R., McKinnon, E., Influence of inhibitory killer immunoglobulin-like receptors and their HLA-C ligands on resolvinghepatitis C virus infection (2007) Tissue Antigens, 69, pp. 237-240Méndez, A., Granda, H., Meenagh, A., Study of KIR genes in tuberculosis patients (2006) Tissue Antigens, 68, pp. 386-389Franceschi, D.A., Mazini, O.S., Rudnick, C.C., Association between killer-cell immunoglobulin-like receptor genotypes and leprosy in Brazil (2008) Tissue Antigens, 72, pp. 478-482Suto, Y., Ishikawa, Y., Kasahara, M., Gene arrangement of the killer cell inhibitory receptor family on human chromosome 19q13.4 detected by fiber-FISH (1998) Immunogenetics, 48, pp. 235-241Green, S., Pichyangkul, S., Vaughn, D.W., Early CD69 expression on peripheral blood lymphocytes from children with dengue hemorrhagic fever (1999) J Infect Dis, 180, pp. 1429-1435Vilches, C., Parham, P., KIR: diverse, rapidly evolving receptors of innate and adaptive immunity (2002) Annu Rev Immunol, 20, pp. 217-251Parham, P., Killer cell immunoglobulin-like receptor diversity: balancing signals in the natural killer cell response (2004) Immunol Lett, 92, pp. 11-13Uhrberg, M., Parham, P., Wernet, P., Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes (2002) Immunogenetics, 54, pp. 221-229Carrington, M., Norman, P., The KIR gene cluster (2003) US Natl Library Med, , http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/mono_003/ch1d1.pdf, Available at:Long, E.O., Rajagopalan, S., HLA class I recognition by killer cell Ig-like receptors (2000) Semin Immunol, 12, pp. 101-108Vales-Gomez, M., Reyburn, H., Strominger, J., Molecular analyses of the interactions between human NK receptors and their HLA ligands (2000) Hum Immunol, 61, pp. 28-38Kulkarni, S., Martin, M.P., Carrington, M., The Yin and Yang of HLA and KIR in human disease (2008) Semin Immunol, 20, pp. 343-352Bashirova, A.A., Martin, M.P., McVicar, D.W., Carrington, M., The killer immunoglobulin-like receptor gene cluster: tuning the genome for defense (2006) Annu Rev Genomics Hum Genet, 7, pp. 277-300Probst, C.M., Bompeixe, E.P., Pereira, N.F., HLA polymorphism and evaluation of European, African, and Amerindian contribution to the white and mulatto populations from Paraná, Brazil (2000) Hum Biol, 72, pp. 597-617John, S.W., Weitzner, G., Rozen, R., Scriver, C.R., A rapid procedure for extracting genomic DNA from leukocytes (1990) Nucleic Acids Res, 192, p. 408Cardozo, D.M., Guelsin, G.A., Clementino, S.L., Extração de DNA a partir de sangue humano coagulado para aplicação nas técnicas de genotipagem de antígenos leucocitários humanos e de receptores semelhantes à imunoglobulina (2009) Rev Soc Bras Med Trop, 42, pp. 651-656(1998) ASHI Standards for Histocompatibility Testing, 1998 Membership Directory, , ASHI. Lenexa, Kansas: American Society for Histocompatibility and ImmunogeneticsRudnick, C.C., Guelsin, G.A., Marangon, A.V., Franceschi, D.A., Sell, A.M., Visentainer, J.E., Otimização de metodologia para o estudo de genes KIR (2010) J Bras Patol Med Lab, 46, pp. 215-224Yindom, L.M., Forbes, R., Aka, P., Killer-cell immunoglobulin-like receptors and malaria caused by Plasmodium falciparum in The Gambia (2012) Tissue Antigens, 79, pp. 104-113Pydi, S.S., Sunder, S.R., Venkatasubramanian, S., Kovvali, S., Jonnalagada, S., Valluri, V.L., Killer cell immunoglobulin like receptor gene association withtuberculosis (2013) Hum Immunol, 74, pp. 85-92Luszczek, W., Manczak, M., Cislo, M., Gene for the activating natural killer cell receptor, KIR2DS1, is associated with susceptibility to psoriasis vulgaris (2004) Hum Immunol, 65, pp. 758-766Suzuki, Y., Hamamoto, Y., Ogasawara, Y., Genetic polymorphisms of killer cell immunoglobulin-like receptors are associated with susceptibility to psoriasis vulgaris (2004) J Invest Dermatol, 122, pp. 1133-1136Augusto, D.G., Lobo-Alves, S.C., Melo, M.F., Pereira, N.F., Petzl-Erler, M.L., Activating KIR and HLA Bw4 ligands are associated to decreased susceptibility to pemphigus foliaceus, an autoimmune blistering skin disease (2012) PLoS ONE, 7, pp. e39991Diaz-Pena, R., Vidal-Castineira, J.R., Alonso-Arias, R., Association of the KIR3DS1*013 and KIR3DL1*004 alleles with susceptibility to ankylosing spondylitis (2010) Arthritis Rheum, 62, pp. 1000-1006Karabon, L., Jedynak, A., Giebel, S., KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic leukemia and the clinical course of disease (2011) Tissue Antigens, 78, pp. 129-138Stern, M., Opelz, G., Döhler, B., Hess, C., Natural killer-cell receptor polymorphisms and posttransplantation non-Hodgkin lymphoma (2010) Blood, 115, pp. 3960-3965Middleton, D., Vilchez, J.R., Cabrera, T., Analysis of KIR gene frequencies in HLA class I characterized bladder, colorectal and laryngeal tumours (2007) Tissue Antigens, 69, pp. 220-226Wauquier, N., Padilla, C., Becquart, P., Leroy, E., Vieillard, V., Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection (2010) Immunogenetics, 62, pp. 767-771Zhi-Ming, L., Yu-Lian, J., Zhao-Lei, F., Polymorphisms of killer cell immunoglobulin-like receptor gene: possible association with susceptibility to or clearance of hepatitis B virus infection in Chinese Han population (2007) Croat Med, 6, pp. 800-806Carr, W.H., Pando, M.J., Parham, P., KIR3DL1 polymorphisms that affect NK cell inhibition by HLA-Bw4 ligand (2005) J Immunol, 175, pp. 5222-5229Khakoo, S.I., Thio, C.L., Martin, M.P., HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection (2004) Science, 305, pp. 872-874Gazit, R., Garty, B.Z., Monselise, Y., Expression of KIR2DL1 on the entire NK cell population: a possible novel immunodeficiency syndrome (2004) Blood, 103, pp. 1965-196

Agent-Based Methods for Simulation of Epidemics with a Low Number of Infected Persons

Part 1: Information & Communication Technology-EurAsia Conference 2014, ICT-EurAsia 2014International audienceModeling of infectious diseases with a low number of infections is a task that often arises since most real epidemics affect only a small fraction of the population. Agent-based methods simulate individuals and their behavior. When the model is simulated, the epidemic automatically arises without being explicitly defined. Surprisingly, it is not easy to produce such epidemics with small infection numbers. Instead, it needs model improvements to accomplish that task. In this paper, we show different extensions, addressing the person’s behavior, the pathogen’s behavior and the environmental impacts. It turns out that the discussed improvements have different consequences. Hence, they need to be used deliberately to overcome modeling issues of a specific epidemic in an appropriate and valid way. Even more, these improvements address the underlying behavior of epidemics and hence have the ability to provide a deeper insight into the real spreading process of a disease