- Email: [email protected]
93-P
110
92-P
Abstracts / Human Immunology 73 (2012) 49–167
KIR2DS2 GENE CONFERS SUSCEPTIBILITY TO LEPROMATOUS LEPROSY (LL) IN MEXICAN PATIENTS. Carmen Alaez 1, Hilario Flores-A 1, Andrea Munguía 1, Araceli Rodríguez 1, David García 1, Myrna Rodríguez 2, Fermín Jurado 2, Obdulia Rodríguez 2, David Senitzer 3, Clara Gorodezky 1. 1 Dept. of Immunology & Immunogenetics, InDRE, Secretary of Health, Mexico City, Mexico; 2 Dermatology, Centro Dermatológico ‘‘Dr. Ladislao de la Pascua’’, Mexico City, Mexico; 3 HLA Laboratory, City of Hope National Medical Center, Duarte, CA, USA. Aim: Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae that occurs primarily in developing countries in tropical and warm temperate regions. The disease displays an immunological spectrum ranging from tuberculoid leprosy (TT) to LL, showing a complete absence of a specific cellular immune response. We and others have published the contribution of HLA Class II genes in LL expression and the participation of HLA-DQ alleles as Is genes. The goal of this study was to investigate the role of KIR genes in the expression of leprosy in Mexican LL patients. Methods: One hundred and six LL patients and 124 healthy controls from the same endemic area were included. LL was diagnosed according to clinical, immunologic and histological criteria. DNA was extracted from peripheral blood. Typing of 14 KIR genes was done using a SSP system with four multiplex reactions. HLA typing was performed using a Luminex PCR-SSOP method. The frequency of each KIR gene was determined by direct counting. A & B haplotypes were deduced from the genotype data. The statistical comparison was done using the X2Y. Results: The presence of the activating gene 2DS2 was found associated with susceptibility to LL (Gf = 59.43% in P. Vs. 43.54% in C., p = 0.02, OR = 1.89). No differences were found in the A or B haplotype groups or their combinations. The KIR-HLA gene combinations were not found deviated; the C4 and T4 cluster depicted no differences either. Conclusions: Our results confirm the involvement of KIR genes in susceptibility to LL, with a variable contribution depending on ethnicity. In a study done in Brazilian patients, 2DS2 was found significantly increased in TT; the authors suggested a possible protective role against the severe form of leprosy. Nonetheless, in Mexicans, 2DS2 is associated with LL. An enhanced NK and T cells activation may promote bacilli dissemination and contribute to the severity in LL, due to the release of cytokines that suppress the CMI and the innate response to the infection.
93-P
HLA HAPLOTYPE FREQUENCIES AND MATCH RATES FOR THE CANADIAN ONEMATCH REGISTRY. Loren Gragert 1, Martin Maiers 1, Sue Smith 2, Yves Garcia 2, Alan DeKoven 2, Meagan Green 2, Donna Killeen 2, Beth Amer 2, Jennifer Philippe 2, Sofia Tavoularis 3,4. 1 Bioinformatics Research, National Marrow Donor Program, Minneapolis, MN, USA; 2 OneMatch Stem Cell and Marrow Network, Canadian Blood Services, Ottawa, Canada; 3 Canadian Blood Services, Head Office, Ottawa, Canada; 4 University of Ottawa, Faculty of Medicine, Ottawa, Canada. Aim: The HLA match rates for the populations served by the Canadian OneMatch registry have not yet been well ascertained. We aimed to use population haplotype frequencies to project HLA match rates for this registry of over 300,000 adult donors and estimate the impact of developing a new cord blood bank. Methods: We calculated high-resolution HLA ACBDRB1 haplotype frequencies from 141,405 OneMatch donors typed by DNA methods, resolving both allelic and phase ambiguity using the EM algorithm. Because of population substructure in Aboriginals, we divided the Aboriginal peoples of Western provinces from Eastern provinces. Using frequencies from 13 Canadian sub-populations, we estimated HLA match rates for five years of increasing adult donor registry size and for the establishment and growth of a nascent cord inventory. Matching models considered availability for adult donors and cell dose requirements for cord of 2.5 107 TNC/kg. Results: Allele-level 8/8 HLA match rates for patients searching for adult donors ranged from 2% for Blacks to 46% for Caucasians. Estimated 7/8 match rates ranged from 12% for Blacks to 86% for Caucasians. We expect that 8/8 and 7/8 match rates will improve by 1-2% per population per year through 2019. Estimated 4/6 match rates for pediatric patients who also search the cord inventory after accrual of 20,000 units ranged from 88% for Blacks to 99% for Caucasians, a substantial marginal benefit. Conclusions: Continued recruitment of adult donors will improve HLA match rates at a steady pace, while development of a cord blood inventory has the potential to close current gaps in stem cell availability, especially for minorities. When analyzing indigenous populations, it is important to consider dividing populations into geographical regions to avoid error in matching models due to population substructure. Recruitment strategy must also be considered in the global context, and we encourage application of similar matching models to all stem cell registries worldwide.
92-P
Abstracts / Human Immunology 73 (2012) 49–167
KIR2DS2 GENE CONFERS SUSCEPTIBILITY TO LEPROMATOUS LEPROSY (LL) IN MEXICAN PATIENTS. Carmen Alaez 1, Hilario Flores-A 1, Andrea Munguía 1, Araceli Rodríguez 1, David García 1, Myrna Rodríguez 2, Fermín Jurado 2, Obdulia Rodríguez 2, David Senitzer 3, Clara Gorodezky 1. 1 Dept. of Immunology & Immunogenetics, InDRE, Secretary of Health, Mexico City, Mexico; 2 Dermatology, Centro Dermatológico ‘‘Dr. Ladislao de la Pascua’’, Mexico City, Mexico; 3 HLA Laboratory, City of Hope National Medical Center, Duarte, CA, USA. Aim: Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae that occurs primarily in developing countries in tropical and warm temperate regions. The disease displays an immunological spectrum ranging from tuberculoid leprosy (TT) to LL, showing a complete absence of a specific cellular immune response. We and others have published the contribution of HLA Class II genes in LL expression and the participation of HLA-DQ alleles as Is genes. The goal of this study was to investigate the role of KIR genes in the expression of leprosy in Mexican LL patients. Methods: One hundred and six LL patients and 124 healthy controls from the same endemic area were included. LL was diagnosed according to clinical, immunologic and histological criteria. DNA was extracted from peripheral blood. Typing of 14 KIR genes was done using a SSP system with four multiplex reactions. HLA typing was performed using a Luminex PCR-SSOP method. The frequency of each KIR gene was determined by direct counting. A & B haplotypes were deduced from the genotype data. The statistical comparison was done using the X2Y. Results: The presence of the activating gene 2DS2 was found associated with susceptibility to LL (Gf = 59.43% in P. Vs. 43.54% in C., p = 0.02, OR = 1.89). No differences were found in the A or B haplotype groups or their combinations. The KIR-HLA gene combinations were not found deviated; the C4 and T4 cluster depicted no differences either. Conclusions: Our results confirm the involvement of KIR genes in susceptibility to LL, with a variable contribution depending on ethnicity. In a study done in Brazilian patients, 2DS2 was found significantly increased in TT; the authors suggested a possible protective role against the severe form of leprosy. Nonetheless, in Mexicans, 2DS2 is associated with LL. An enhanced NK and T cells activation may promote bacilli dissemination and contribute to the severity in LL, due to the release of cytokines that suppress the CMI and the innate response to the infection.
93-P
HLA HAPLOTYPE FREQUENCIES AND MATCH RATES FOR THE CANADIAN ONEMATCH REGISTRY. Loren Gragert 1, Martin Maiers 1, Sue Smith 2, Yves Garcia 2, Alan DeKoven 2, Meagan Green 2, Donna Killeen 2, Beth Amer 2, Jennifer Philippe 2, Sofia Tavoularis 3,4. 1 Bioinformatics Research, National Marrow Donor Program, Minneapolis, MN, USA; 2 OneMatch Stem Cell and Marrow Network, Canadian Blood Services, Ottawa, Canada; 3 Canadian Blood Services, Head Office, Ottawa, Canada; 4 University of Ottawa, Faculty of Medicine, Ottawa, Canada. Aim: The HLA match rates for the populations served by the Canadian OneMatch registry have not yet been well ascertained. We aimed to use population haplotype frequencies to project HLA match rates for this registry of over 300,000 adult donors and estimate the impact of developing a new cord blood bank. Methods: We calculated high-resolution HLA ACBDRB1 haplotype frequencies from 141,405 OneMatch donors typed by DNA methods, resolving both allelic and phase ambiguity using the EM algorithm. Because of population substructure in Aboriginals, we divided the Aboriginal peoples of Western provinces from Eastern provinces. Using frequencies from 13 Canadian sub-populations, we estimated HLA match rates for five years of increasing adult donor registry size and for the establishment and growth of a nascent cord inventory. Matching models considered availability for adult donors and cell dose requirements for cord of 2.5 107 TNC/kg. Results: Allele-level 8/8 HLA match rates for patients searching for adult donors ranged from 2% for Blacks to 46% for Caucasians. Estimated 7/8 match rates ranged from 12% for Blacks to 86% for Caucasians. We expect that 8/8 and 7/8 match rates will improve by 1-2% per population per year through 2019. Estimated 4/6 match rates for pediatric patients who also search the cord inventory after accrual of 20,000 units ranged from 88% for Blacks to 99% for Caucasians, a substantial marginal benefit. Conclusions: Continued recruitment of adult donors will improve HLA match rates at a steady pace, while development of a cord blood inventory has the potential to close current gaps in stem cell availability, especially for minorities. When analyzing indigenous populations, it is important to consider dividing populations into geographical regions to avoid error in matching models due to population substructure. Recruitment strategy must also be considered in the global context, and we encourage application of similar matching models to all stem cell registries worldwide.