Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolutio...Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.展开更多
目的探讨免疫性血小板输注无效患者血清中人类白细胞抗原(HLA)及人类血小板抗原(HPA)抗体变化的临床意义,分析抗体强度及输注次数对血小板输注效果的影响。方法回顾性纳入95例患者,按抗体类型(HLA型、HPA型、HLA+HPA型)及强度(HLA低/中...目的探讨免疫性血小板输注无效患者血清中人类白细胞抗原(HLA)及人类血小板抗原(HPA)抗体变化的临床意义,分析抗体强度及输注次数对血小板输注效果的影响。方法回顾性纳入95例患者,按抗体类型(HLA型、HPA型、HLA+HPA型)及强度(HLA低/中/高、HPA低/高)分组,对比输注有效率(24 h血小板校正增高指数CCI≤4.5为无效)及CCI水平,分析输注次数与抗体强度相关性。结果纳入的95例患者中,84.21%为HLA抗体阳性,HPA抗体阳性占9.47%,HLA+HPA抗体共占6.32%。HLA型患者中,交叉配型相合血小板输注有效率及24 h CCI水平均显著高于随机血小板输注(P<0.05);HPA型、HLA+HPA型患者中,两种输注方式的有效率及24 h CCI水平对比均无显著差异(P>0.05)。随HLA抗体强度增加,交叉配型相合血小板输注有效率及24 h CCI逐渐降低(P<0.05);中、低强度HLA抗体患者交叉配型相合输注有效率及24 h CCI均显著高于随机输注(P<0.05),高强度HLA抗体患者两种输注方式的有效率及24 h CCI无显著差异(P>0.05)。随机输注组平均次数显著多于交叉配型组(P<0.05),且随机输注次数与HLA抗体强度呈正相关(P<0.05)。结论HLA抗体强度是影响输注效果的关键因素,交叉配型可提高不同强度HLA抗体患者疗效;反复随机输注可能促进HLA抗体升高,HPA抗体影响需扩大样本验证。展开更多
文摘Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.
文摘目的探讨免疫性血小板输注无效患者血清中人类白细胞抗原(HLA)及人类血小板抗原(HPA)抗体变化的临床意义,分析抗体强度及输注次数对血小板输注效果的影响。方法回顾性纳入95例患者,按抗体类型(HLA型、HPA型、HLA+HPA型)及强度(HLA低/中/高、HPA低/高)分组,对比输注有效率(24 h血小板校正增高指数CCI≤4.5为无效)及CCI水平,分析输注次数与抗体强度相关性。结果纳入的95例患者中,84.21%为HLA抗体阳性,HPA抗体阳性占9.47%,HLA+HPA抗体共占6.32%。HLA型患者中,交叉配型相合血小板输注有效率及24 h CCI水平均显著高于随机血小板输注(P<0.05);HPA型、HLA+HPA型患者中,两种输注方式的有效率及24 h CCI水平对比均无显著差异(P>0.05)。随HLA抗体强度增加,交叉配型相合血小板输注有效率及24 h CCI逐渐降低(P<0.05);中、低强度HLA抗体患者交叉配型相合输注有效率及24 h CCI均显著高于随机输注(P<0.05),高强度HLA抗体患者两种输注方式的有效率及24 h CCI无显著差异(P>0.05)。随机输注组平均次数显著多于交叉配型组(P<0.05),且随机输注次数与HLA抗体强度呈正相关(P<0.05)。结论HLA抗体强度是影响输注效果的关键因素,交叉配型可提高不同强度HLA抗体患者疗效;反复随机输注可能促进HLA抗体升高,HPA抗体影响需扩大样本验证。
