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The HLA component of type 1 diabetes
S64
Abstracts
5 89-P
HUMAN T-CELL LYMPHOTROPIC VIRUSES (HTLVI/II) IN MEXICAN MESTIZOS AND NATIVES: MIXTECO, SERI AND LACANDON. RELATIONSHIP WITH HLA-B* Z. Morales, C. Alaez, A. Rodriguez, C. Gorodezky, Dept of Immunol & Immunogenet, InDRE, Mexico City, Mexico HTLVI/ HTLVII are human oncoviridae causally associated with adult T cell leukaemia /lymphoma. They are endemic in Central/South-America where they show geographic clustering: HTLVI among native Amerindians (Andean highlands and Brazilian coast); HTLVII predominates in the lowlands, its prevalence in Yucatan, Mexico is 0.3%. The aim of this study was to assess the prevalence of HTLV I/II antibodies in the Mexican Mestizo and in several native groups: Mixteco from Oaxaca, of the southwest (N⫽55), Seri from Sonora of the northwest (N⫽102), Lacandon from the jungle of Chiapas in the southeast (N⫽175) and Mestizo (N⫽118). We used the Innogenetics INNO-LIA HTLV I/II Score. It allows the detection of HTLV I/II antibodies in serum/plasma. It also differentiates between HTLVI/HTLVII types.The assay uses recombinant/synthetic peptides derived from HTLVI/II immunodominant proteins. The type-specific antigens for HTLV-I (gag p19-I, env gp46-I) and for HTLV-II (env gp46-II) differentiate between types. The intensity of the reaction on the control lines on each strip is the baseline to assign the reactivity for each antigen on that strip. All populations showed negative results except for the Lacandon in whom 1 individual was found positive and 5 were indeterminates (0.03% including the latter). Every individual was typed for DRB1/DQA1/ DQB1 and most of them for A*; B*, C* alleles. Interestingly, the 4/6 Lacandon typed for class I loci, shared B*4002. The data are concordant with those found in Latin America. The expectation was to detect HTLVI/II in the Southeast more than in the rest of Mexico, being a tropical area. The relation with class I alleles in them, agrees with the genetic control of humoral response against viruses.
5 90-P
THE HLA COMPONENT OF TYPE 1 DIABETES Glenys Thomson,1 Ana Maria Valdes,2 Janice S. Dorman,3 Ann Steenkiste,3 Janelle A. Noble,2 Patrick Concannon,4 Anajane G. Smith,5 Hansen John,5 Ake Lernmark,6 Alberto Pugliese7, 1Integrative Biology, University of California, Berkeley, CA, USA; 2CHORI, Oakland, CA, USA; 3Public Health, University of Pittsburgh, Pittsburgh, PA, USA; 4Immunology, University of Washington, Seattle, WA, USA; 5Fred Hutchinson, University of Washington, Seattle, WA, USA; 6 Medicine, University of Washington, Seattle, WA, USA; 7Diabetes, University of Miami, Miami, FL, USA Microsatellite data from the 13th International Histocompatibility Workshop type 1 diabetes case/control and family samples have been analyzed to detect the role of disease genes in the HLA region in addition to the DR-DQ genes. Some significant and consistent results were found; but whereas the data implicate additional genes in the HLA region they also show extensive heterogeneity reminiscent of non-HLA genes in complex diseases. Heterogeneity of DR3 haplotypes, with overtransmission of DR3-B18 haplotypes carrying a D6S273 allele, has been found, in agreement with previous reports. Heterogeneity of the protective effect of DRB1*1501 DQB1*0602 haplotypes has been found in a Swedish data set with an allele at D6S265 being associated with weaker protection. In a US family data set, statistically significant age of onset effects at class III markers have been identified that are not due to linkage disequilibrium with class I alleles known to affect age of onset. HLA DR-DQ haplotypes and genotypes show consistency in rank order of predisposing, neutral, and protective effects across ethnic groups. The amino acids consistently involved in disease in different populations have been identified. All type 1 diabetes genetic factors in the HLA region can be identified with large sample sizes and cross ethnic studies.
Abstracts
5 89-P
HUMAN T-CELL LYMPHOTROPIC VIRUSES (HTLVI/II) IN MEXICAN MESTIZOS AND NATIVES: MIXTECO, SERI AND LACANDON. RELATIONSHIP WITH HLA-B* Z. Morales, C. Alaez, A. Rodriguez, C. Gorodezky, Dept of Immunol & Immunogenet, InDRE, Mexico City, Mexico HTLVI/ HTLVII are human oncoviridae causally associated with adult T cell leukaemia /lymphoma. They are endemic in Central/South-America where they show geographic clustering: HTLVI among native Amerindians (Andean highlands and Brazilian coast); HTLVII predominates in the lowlands, its prevalence in Yucatan, Mexico is 0.3%. The aim of this study was to assess the prevalence of HTLV I/II antibodies in the Mexican Mestizo and in several native groups: Mixteco from Oaxaca, of the southwest (N⫽55), Seri from Sonora of the northwest (N⫽102), Lacandon from the jungle of Chiapas in the southeast (N⫽175) and Mestizo (N⫽118). We used the Innogenetics INNO-LIA HTLV I/II Score. It allows the detection of HTLV I/II antibodies in serum/plasma. It also differentiates between HTLVI/HTLVII types.The assay uses recombinant/synthetic peptides derived from HTLVI/II immunodominant proteins. The type-specific antigens for HTLV-I (gag p19-I, env gp46-I) and for HTLV-II (env gp46-II) differentiate between types. The intensity of the reaction on the control lines on each strip is the baseline to assign the reactivity for each antigen on that strip. All populations showed negative results except for the Lacandon in whom 1 individual was found positive and 5 were indeterminates (0.03% including the latter). Every individual was typed for DRB1/DQA1/ DQB1 and most of them for A*; B*, C* alleles. Interestingly, the 4/6 Lacandon typed for class I loci, shared B*4002. The data are concordant with those found in Latin America. The expectation was to detect HTLVI/II in the Southeast more than in the rest of Mexico, being a tropical area. The relation with class I alleles in them, agrees with the genetic control of humoral response against viruses.
5 90-P
THE HLA COMPONENT OF TYPE 1 DIABETES Glenys Thomson,1 Ana Maria Valdes,2 Janice S. Dorman,3 Ann Steenkiste,3 Janelle A. Noble,2 Patrick Concannon,4 Anajane G. Smith,5 Hansen John,5 Ake Lernmark,6 Alberto Pugliese7, 1Integrative Biology, University of California, Berkeley, CA, USA; 2CHORI, Oakland, CA, USA; 3Public Health, University of Pittsburgh, Pittsburgh, PA, USA; 4Immunology, University of Washington, Seattle, WA, USA; 5Fred Hutchinson, University of Washington, Seattle, WA, USA; 6 Medicine, University of Washington, Seattle, WA, USA; 7Diabetes, University of Miami, Miami, FL, USA Microsatellite data from the 13th International Histocompatibility Workshop type 1 diabetes case/control and family samples have been analyzed to detect the role of disease genes in the HLA region in addition to the DR-DQ genes. Some significant and consistent results were found; but whereas the data implicate additional genes in the HLA region they also show extensive heterogeneity reminiscent of non-HLA genes in complex diseases. Heterogeneity of DR3 haplotypes, with overtransmission of DR3-B18 haplotypes carrying a D6S273 allele, has been found, in agreement with previous reports. Heterogeneity of the protective effect of DRB1*1501 DQB1*0602 haplotypes has been found in a Swedish data set with an allele at D6S265 being associated with weaker protection. In a US family data set, statistically significant age of onset effects at class III markers have been identified that are not due to linkage disequilibrium with class I alleles known to affect age of onset. HLA DR-DQ haplotypes and genotypes show consistency in rank order of predisposing, neutral, and protective effects across ethnic groups. The amino acids consistently involved in disease in different populations have been identified. All type 1 diabetes genetic factors in the HLA region can be identified with large sample sizes and cross ethnic studies.