Correlation of mixed lymphocyte culture with chronic graft-versus-host disease following allogeneic stem cell transplantation

The purpose of the present study was to evaluate the mixed lymphocyte culture as a predictive assay of acute and chronic graft-versus-host disease (GVHD). We studied 153 patients who received a first bone marrow transplantation from human leukocyte antigen-identical siblings. Acute GVHD was observed in 26 of 128 (20.3%) patients evaluated and chronic GVHD occurred in 60 of 114 (52.6%). One-way mixed lymphocyte culture (MLC) assays were performed by the standard method. MLC results are reported as the relative response (RR) from donor against patient cells. The responses ranged from -47.0 to 40.7%, with a median of 0.5%. The Kaplan-Meier probability of developing GVHD was determined for patients with positive and negative MLC. There was no significant difference in incidence of acute GVHD between the groups studied. However, the incidence of chronic GVHD was higher in recipients with RR >4.5% than in those with RR 4.5%), 2.9 for those who received peripheral blood progenitor cells as a graft, and 2.2 for patients who developed previous acute GVHD. MLC was not useful for predicting acute GVHD, but MLC with RR >4.5% associated with other risk factors could predict the development of chronic GVHD, being of help for the prevention and/or treatment of this late complication.56757

Role Of Cytokines In The Immunopathogenesis Of Graft-versus-host Disease [papel Das Citocinas Na Imunopatogênese Da Doença Do Enxerto Contra O Hospedeiro]

Stem cell transplantation is the first line treatment of many hematological diseases and primary immunodeficiencies. Graft-versus-host disease (GVHD) is still a severe complication after allogeneic transplantation and the main cause of mortality and morbidity. The study of the pathogenesis of GVHD may help to develop ways to prevent the disease, as well as to choose adequate immunosuppressant therapies. This study discusses the main immunological components involved in the pathogenesis of acute and chronic GVHD, with emphasis on the participation of cytokines and their control.302142152Jaksch, M., Mattsson, J., The pathophysiology of acute graft-versus-host disease (2005) Scand J Immunol, 61 (5), pp. 398-409Ferrara, J.L., Yanik, G., Acute graft versus host disease: Pathophysiology, risk factors, and prevention strategies. Clin Adv Hematol Oncol (2005), 3 (5). , 415-9,428Niederwieser, D., Herold, M., Woloszczuk, W., Endogenous IFN-gamma during human bone marrow transplantation. 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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

Genetic Polymorphisms Of Rh, Kell, Duffy And Kidd Systems In A Population From The State Of Paraná, Southern Brazil

Background: Red blood group genes are highly polymorphic and the distribution of alleles varies among different populations and ethnic groups. Aim: To evaluate allele polymorphisms of the Rh, Kell, Duffy and Kidd blood group systems in a population of the State of Paraná Methods: Rh, Kell, Duffy and Kidd blood group polymorphisms were evaluated in 400 unrelated blood or bone marrow donors from the northwestern region of Paraná State between September 2008 and October 2009. The following techniques were used: multiplex-polymerase chain reaction genotyping for the identification of the RHD gene and RHCE C/c genotype; allele-specific polymerase chain reaction for the RHDΨ and restriction fragment length polymorphism polymerase chain reaction for the RHCEE/e, KEL, FY-GATA and JK alleles. Results: These techniques enabled the evaluation of the frequencies of Rh, Kell, Duffy and Kidd polymorphisms in the population studied, which were compared to frequencies in two populations from the eastern region of São Paulo State. Conclusion: The RHCE c/c, FY A/FY B, GATA-33 T/T, JK B/JK B genotypes were more prevalent in the population from Paraná, while RHCE C/c, FY B/FY B, GATA-33 C/C, JK A/JK B genotypes were more common in the populations from São Paulo.3312125Daniels, G., Castilho, L., Flegel, W.A., Fletcher, A., Garratty, G., Levene, C., International Society of Blood Transfusion Committee on Terminology for red blood cell surface antigens: Macao report (2009) Vox Sang, 96 (2), pp. 153-156Hellberg, A., Chester, M.A., Olsson, M.L., Two previously proposed P1/ P2-differentiating and nine novel polymorphisms at the A4GALT (Pk) locus do not correlate with the presence of the P1 blood group antigen (2005) BMC Genet, 6, p. 49Tilley, L., Green, C., Daniels, G., Sequence variation in the 5' untranslated region of the human A4GALT gene is associated with, but does not define, the P1 blood group polymorphism (2006) Vox Sang, 90 (3), pp. 198-203Yip, S.P., Sequence variation at the human ABO locus (2002) Ann Hum Genet, 66 (Pt1), pp. 1-27Daniels, G., The molecular genetics of blood group polymorphism (2009) Hum Genet, 126 (6), pp. 729-742Lee, S., Molecular basis of Kell blood group phenotypes (1997) Vox Sang, 73 (1), pp. 1-11. , Erratum in: Vox Sang 1998;74(1):58Lee, S., Zambas, E.D., Marsh, W.L., Redman, C.M., The human Kell blood group gene maps to chromosome 7q33 and its expression is restricted to erythroid cells (1993) Blood, 81 (10), pp. 2804-2809Pruenster, M., Rot, A., Throwing light on DARC (2006) Biochem Soc Trans, 34 (Pt6), pp. 1005-1008Miller, L.H., Mason, S.J., Dvorak, J.A., McGinniss, M.H., Rothman, I.K., Erythrocyte receptors for (Plasmodium knowlesi) malaria: Duffy blood group determinants (1975) Science, 189 (4202), pp. 561-563You, G., Smith, C.P., Kanai, Y., Lee, W.-S., Stelzner, M., Hediger, M.A., Cloning and characterization of the vasopressin-regulated urea transporter (1993) Nature, 365 (6449), pp. 844-847Olivès, B., Merriman, M., Bailly, P., Bain, S., Barnett, A., Todd, J., The molecular basis of the Kidd blood group polymorphism and its lack of association with type 1 diabetes susceptibility (1997) Hum Mol Genet, 6 (7), pp. 1017-1020Lin, Y., Pavenski, K., Saidenberg, E., Branch, D.R., Blood group antigens and normal red blood cell physiology: A Canadian blood services research and development symposium (2009) Transfus Med Rev, 23 (4), pp. 292-309Singleton, B.K., Green, C.A., Avent, N.D., Martin, P.G., Smart, E., Daka, A., The presence of an RHD pseudogene containing a 37 base pair duplication phenotype and a nonsense mutation in africans with the Rh D-negative blood group (2000) Blood, 95 (1), pp. 12-18Rios, M., Cash, K., Strupp, A., Uehlinger, J., Reid, M.E., DNA from urine sediment or buccal cells can be used for blood group molecular genotyping (1999) Immunohematology, 15 (2), pp. 61-65Reid, M.E., Rios, M., Yazdanbakhsh, K., Applications of molecular biology techniques to transfusion medicine (2000) Semin Hematol, 37 (2), pp. 166-176Ribeiro, K.R., Guarnieri, M.H., da Costa, D.C., Costa, F.F., Pellegrino Jr., J., Castilho, L., DNA array analysis for red blood cell antigens facilitates the transfusion support with antigen-matched blood in patients with sickle cell disease (2009) Vox Sang, 97 (2), pp. 147-152Pellegrino Jr., J., Castilho, L., Rios, M., de Souza, C.A., Blood group genotyping in a population of highly diverse ancestry (2001) J Clin Lab Anal, 15 (1), pp. 8-13Svejgaard, A., Jersild, C., Nielsen, S., Bodmer, W.F., HLA and disease. Statistical genetic consideration (1974) Tissue Antigens, 4 (2), pp. 95-105Parra, F.C., Amado, R.C., Lambertucci, J.R., Rocha, J., Antunes, C.M., Pena, S.D.J., Color and genomic ancestry in Brazilians (2003) Proc Natl Acad Sci USA, 100 (1), pp. 177-182Carvalho-Silva, D.R., Santos, F.R., Rocha, J., Pena, S.D., The phylogeography of Brazilian Y-chromosome lineages (2001) Am J Hum Genet, 68 (1), pp. 281-286Probst, C.M., Bompeixe, E.P., Pereira, N.F., de O Dalalio, M.M., Visentainer, J.E., Tsuneto, L.T., HLA polymorphism and evaluation of European, African, and Amerindian contribution to the white and mulatto populations from Paraná, Brazil (2000) Hum Biol, 72 (4), pp. 597-617Cavasini, C.E., de Mattos, L.C., Couto, A.A., Couto, V.S., Gollino, Y., Moretti, L.J., Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region (2007) Malar J, 6, pp. 167-174Visentainer, J.E., Sell, A.M., da Silva, G.C., Cavichioli, A.D., Franceschi, D.S., Lieber, S.R., TNF, IFNG, IL6, IL10 and TGFB1 gene polymorphisms in South and Southeast Brazil (2008) Int J Immunogenet, 35 (4-5), pp. 287-29

Association of leprosy with HLA-DR2 in a Southern Brazilian population

The association between HLA specificities and leprosy was investigated in a Southern Brazilian population. One hundred and twenty-one patients and 147 controls were typed for HLA-A, B, Cw, DR and DQ. Patients were subdivided into the following subgroups, according to clinical, histological and immunological criteria: lepromatous (N = 55), tuberculoid (N = 32), dimorphous (N = 20), and indeterminate (N = 14). The frequencies of HLA specificities were compared between the total group of patients and controls, and between the same controls and each subgroup of patients. After correction of the probabilities, deviations were not significant, except for the DR2 specificity, which presented a frequency of 44.2% in the total group of patients and 56.3% in the subgroup of individuals with the tuberculoid form of the disease, compared to 23.3% in the controls. Stratified analysis showed that the increased DR2 frequency in the total group of patients was due to the subgroups with the tuberculoid and dimorphous forms. The relative risk of tuberculoid leprosy for DR2-positive individuals was 4.2, and the etiologic fraction of DR2 was 0.429. In conclusion, a positive association of the DR2 specificity with the tuberculoid form of leprosy, but not with the lepromatous, dimorphous, or indeterminate forms, was demonstrated in this Southern Brazilian populatio