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Abstracts
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S171
NO DIFFERENCES IN THE FREQUENCIES OF HLA-DRB3/B4/B5 HETEROZYGOSITY BETWEEN MALES AND FEMALES IN HEALTHY KOREAN ADULTS Eun Young Song,1 Eun Youn Roh,2 Myoung Hee Park.2 1Department of Laboratory Medicine, Konkuk University Hospital, Seoul, Korea; 2 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea Aim: HLA class II haplotypes often contain a second expressed HLA-DRB locus, which can be either HLADRB3, DRB4 or DRB5. These encode the supertypical specificities and mark the ancestral lineages. There have been suggestions of relevance of one of these lineages in male-specific susceptibility to childhood leukemia and the epidemiological association between childhood leukemia and fetal loss. Recently, there also has been one report of heterozygote excess in Welsh male newborns suggesting a possibility of male-specific MHC-mediated prenatal selection [1]. While there was no significant change in heterozygosity rates between males and females at DRB1 loci, the proportion of males carrying two DRB1 specificities from two different ancestral lineages was significantly increased (53.7% vs 39.3%, p⫽0.003), with most marked increase for DRB3/DRB4 heterozygotes. However, it has not been confirmed in any other ethnic groups or in adult population. Methods: We analyzed differences of HLA-DRB3/4/5 heterozygosity rates between males and females among 2,083 healthy Korean adult hematopoietic stem cell donors registered to the KMDP (Korea Marrow Donor Program): 1,111 males and 972 females, median age 22, age range 17-47. HLA-DRB1/B3/B4/B5 DNA typing was performed using Dynal RELITM HLA-DRB SSO kit (Dyanl Biotech, Wirral, U.K.). Scope: There was no significant change in the proportion of males carrying two DRB1 specificities from different ancestral lineages, namely DRB3, DRB4 and DRB5 (Table 1). Conclusions: Our results suggest that it could be due to some ethnic differences. Another possible explanation is that some postnatal selection events on DRB3/B4/B5 heterozygotes can make a difference between newborns and adults. Further studies on Korean newborns are needed to answer these questions. Reference: 1. Dorak MT, Lawson T, Machulla HK, et al. Increased heterozygosity for MHC class II lineages in newborn males. Genes Immun 2002;3:263-9. TABLE 1: Frequencies of DRB3/4/5 Heterozygosity in Healthy Korean Adults Males (n⫽1,111) Heterozygotes DRB3/B4 DRB3/B5 DRB4/B5 Total
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n 246 87 111 444
% 22.1% 7.8% 10.0% 40.0%
Females (n⫽972) n 253 75 92 420
% 26.0% 7.7% 9.5% 43.2%
ASSOCIATION OF HLA CLASS I AND CLASS II WITH LEUKEMIA IN A BRAZILIAN POPULATION Jeane E.L. Visentainer,1 Lu´cia A. Barion,1 Cintia R. Sossai,2 Giuliana V. Testa,2 Sofia R. Lieber,2 Ligia B.L. Persoli,2 Silvia B.D. Marques,2 Afonso C. Vigorito,2 Francisco J.P. Aranha,2 Katia A.B. Eid,2 Gislaine B. Oliveira,2 Ca´rmino A. de Souza.2 1Clinical Analysis Department, Maringa´ State University, Maringa´, Parana´, Brazil; 2Hematology and Hemotherapy Center, Campinas State University, Campinas, SP, Brazil Aim: The main of this study was to investigate the frequency of HLA class-I antigens and class-II alleles in 164 Brazilian patients with leukemia attending the Hematology and Hemotherapy Center at Campinas State University. Methods: HLA class-I typing was performed using standard microlymphocytotoxicity method and HLA class-II typing was performed using polymerase chain reaction with sequence-specific of primers (PCR-SSP). Scope: In the patients with acute lymphocytic leukemia (ALL), the frequencies of HLA-B45 and HLA-B56 antigens were higher (P ⫽ 0.02, OR ⫽ 3.13, 95%IC ⫽ 0.94-10.44; P ⫽ 0.03; OR ⫽ 3.61, 95%IC ⫽ 0.4727.64, respectively), as compared with healthy individuals. In the patients with acute myeloid leukemia (AML), the frequency of HLA-B7 (P ⫽ 0.01, OR ⫽ 2.41, 95%IC ⫽ 1.25-4.67) was higher than those in healthy individuals. In patients with chronic myeloid leukemia (CML), there was positive association with the HLA-B45 antigen (P⫽ 0.01, OR ⫽ 3.29, 95%IC ⫽ 1.46-7.40) and HLA-DRB1*04 (P ⫽ 0.002, OR ⫽ 2.17, 95%IC ⫽ 1.36-3.46) and HLA-DRB1*08 alleles (P ⫽ 0.004, OR ⫽ 2.36, 95%IC ⫽ 1.34-4.16). Conclusions: The present results suggest positive associations between certain HLA class-I antigens and class-II alleles and leukemias. These preliminary data may be useful for further study on the mechanisms of leukemia pathogenesis.
189-P
S171
NO DIFFERENCES IN THE FREQUENCIES OF HLA-DRB3/B4/B5 HETEROZYGOSITY BETWEEN MALES AND FEMALES IN HEALTHY KOREAN ADULTS Eun Young Song,1 Eun Youn Roh,2 Myoung Hee Park.2 1Department of Laboratory Medicine, Konkuk University Hospital, Seoul, Korea; 2 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea Aim: HLA class II haplotypes often contain a second expressed HLA-DRB locus, which can be either HLADRB3, DRB4 or DRB5. These encode the supertypical specificities and mark the ancestral lineages. There have been suggestions of relevance of one of these lineages in male-specific susceptibility to childhood leukemia and the epidemiological association between childhood leukemia and fetal loss. Recently, there also has been one report of heterozygote excess in Welsh male newborns suggesting a possibility of male-specific MHC-mediated prenatal selection [1]. While there was no significant change in heterozygosity rates between males and females at DRB1 loci, the proportion of males carrying two DRB1 specificities from two different ancestral lineages was significantly increased (53.7% vs 39.3%, p⫽0.003), with most marked increase for DRB3/DRB4 heterozygotes. However, it has not been confirmed in any other ethnic groups or in adult population. Methods: We analyzed differences of HLA-DRB3/4/5 heterozygosity rates between males and females among 2,083 healthy Korean adult hematopoietic stem cell donors registered to the KMDP (Korea Marrow Donor Program): 1,111 males and 972 females, median age 22, age range 17-47. HLA-DRB1/B3/B4/B5 DNA typing was performed using Dynal RELITM HLA-DRB SSO kit (Dyanl Biotech, Wirral, U.K.). Scope: There was no significant change in the proportion of males carrying two DRB1 specificities from different ancestral lineages, namely DRB3, DRB4 and DRB5 (Table 1). Conclusions: Our results suggest that it could be due to some ethnic differences. Another possible explanation is that some postnatal selection events on DRB3/B4/B5 heterozygotes can make a difference between newborns and adults. Further studies on Korean newborns are needed to answer these questions. Reference: 1. Dorak MT, Lawson T, Machulla HK, et al. Increased heterozygosity for MHC class II lineages in newborn males. Genes Immun 2002;3:263-9. TABLE 1: Frequencies of DRB3/4/5 Heterozygosity in Healthy Korean Adults Males (n⫽1,111) Heterozygotes DRB3/B4 DRB3/B5 DRB4/B5 Total
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n 246 87 111 444
% 22.1% 7.8% 10.0% 40.0%
Females (n⫽972) n 253 75 92 420
% 26.0% 7.7% 9.5% 43.2%
ASSOCIATION OF HLA CLASS I AND CLASS II WITH LEUKEMIA IN A BRAZILIAN POPULATION Jeane E.L. Visentainer,1 Lu´cia A. Barion,1 Cintia R. Sossai,2 Giuliana V. Testa,2 Sofia R. Lieber,2 Ligia B.L. Persoli,2 Silvia B.D. Marques,2 Afonso C. Vigorito,2 Francisco J.P. Aranha,2 Katia A.B. Eid,2 Gislaine B. Oliveira,2 Ca´rmino A. de Souza.2 1Clinical Analysis Department, Maringa´ State University, Maringa´, Parana´, Brazil; 2Hematology and Hemotherapy Center, Campinas State University, Campinas, SP, Brazil Aim: The main of this study was to investigate the frequency of HLA class-I antigens and class-II alleles in 164 Brazilian patients with leukemia attending the Hematology and Hemotherapy Center at Campinas State University. Methods: HLA class-I typing was performed using standard microlymphocytotoxicity method and HLA class-II typing was performed using polymerase chain reaction with sequence-specific of primers (PCR-SSP). Scope: In the patients with acute lymphocytic leukemia (ALL), the frequencies of HLA-B45 and HLA-B56 antigens were higher (P ⫽ 0.02, OR ⫽ 3.13, 95%IC ⫽ 0.94-10.44; P ⫽ 0.03; OR ⫽ 3.61, 95%IC ⫽ 0.4727.64, respectively), as compared with healthy individuals. In the patients with acute myeloid leukemia (AML), the frequency of HLA-B7 (P ⫽ 0.01, OR ⫽ 2.41, 95%IC ⫽ 1.25-4.67) was higher than those in healthy individuals. In patients with chronic myeloid leukemia (CML), there was positive association with the HLA-B45 antigen (P⫽ 0.01, OR ⫽ 3.29, 95%IC ⫽ 1.46-7.40) and HLA-DRB1*04 (P ⫽ 0.002, OR ⫽ 2.17, 95%IC ⫽ 1.36-3.46) and HLA-DRB1*08 alleles (P ⫽ 0.004, OR ⫽ 2.36, 95%IC ⫽ 1.34-4.16). Conclusions: The present results suggest positive associations between certain HLA class-I antigens and class-II alleles and leukemias. These preliminary data may be useful for further study on the mechanisms of leukemia pathogenesis.