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
The restriction fragnent length polymorphisms （RFLPs） of HLA class I genes in 104 unrelated healthy Chinese individuals were analyzed with Southern blot assay. The DNAs from peripheral blood leucocytes were digested...The restriction fragnent length polymorphisms （RFLPs） of HLA class I genes in 104 unrelated healthy Chinese individuals were analyzed with Southern blot assay. The DNAs from peripheral blood leucocytes were digested with EcoRI, EcoRV and XbaI respectively, and hybridized with <sup>32</sup>P-labeled HLA class I probe （ 1.4Kb, B7 cDNA ）. The results showed that 3 EcoRI fragments （13.7, 8.1 and 5.2 Kb ）, 3 EcoR V fragments （11.3, 7.8 and 4.1 Kb） and 7 Xbal fragmnents （21.9, 19.2, 16.3, 6.0, 3.8, 1.8 and 1.5 Kb） were polymorphic. Ten of the fragments were found to be correlated significantly with the serologically de fined antigen specificities. The significance of this kind of correlation is discussed.展开更多
Objective： To investigate the expression change of human leukocyte antigen （HLA） class I on human peripheral blood mononuclear ceils （PBMCs） at both mRNA and protein levels, and to evaluate its roles in the devel...Objective： To investigate the expression change of human leukocyte antigen （HLA） class I on human peripheral blood mononuclear ceils （PBMCs） at both mRNA and protein levels, and to evaluate its roles in the development of colorectal cancer （CRC）. Methods： In the present study, 50 patients with CRC, 35 patients with benign colorectal lesion and 42 healthy volunteers were enrolled. Expression levels of HLA class I mRNA and protein were determined using real-time quantitative reverse transcription PCR （RT-PCR） and flow cytometry analysis, respectively. Results： The expression levels of HLA class I mRNA and proteins were not influenced by age and gender. The relative ratios of HLA class I mRNA were 0.99±0.27 in healthy controls, 0.76±0.19 in benign patients, and 0.48±0.21 in CRC patients. Mean fluorescence intensities of HLA class I were 145.58±38.14 in healthy controls, 102.05±35.98 in benign patients and 87.44±34.01 in CRC patients. HLA class I on PBMCs was significantly down-regulated at both mRNA and protein levels in patients with stage III and IV CRC. CRC patients with lymph node metastasis also showed a decreased HLA class I expression at protein level. Conclusion： HLA class I expressions on PBMCs are associated with staging of CRC and lymph node metastasis. Monitoring the expression of HLA class I on PBMCs may provide useful information for diagnosis and metastasis judgement of CRC.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The restriction fragnent length polymorphisms （RFLPs） of HLA class I genes in 104 unrelated healthy Chinese individuals were analyzed with Southern blot assay. The DNAs from peripheral blood leucocytes were digested with EcoRI, EcoRV and XbaI respectively, and hybridized with <sup>32</sup>P-labeled HLA class I probe （ 1.4Kb, B7 cDNA ）. The results showed that 3 EcoRI fragments （13.7, 8.1 and 5.2 Kb ）, 3 EcoR V fragments （11.3, 7.8 and 4.1 Kb） and 7 Xbal fragmnents （21.9, 19.2, 16.3, 6.0, 3.8, 1.8 and 1.5 Kb） were polymorphic. Ten of the fragments were found to be correlated significantly with the serologically de fined antigen specificities. The significance of this kind of correlation is discussed.
基金supported by Shandong Province Natural Science Foundation (No. Y2008C104)Shandong Province Science Foundation for Key Program (No. 2007GG20002027,2008GG2NS02016 and 2009GG10002043)
文摘Objective： To investigate the expression change of human leukocyte antigen （HLA） class I on human peripheral blood mononuclear ceils （PBMCs） at both mRNA and protein levels, and to evaluate its roles in the development of colorectal cancer （CRC）. Methods： In the present study, 50 patients with CRC, 35 patients with benign colorectal lesion and 42 healthy volunteers were enrolled. Expression levels of HLA class I mRNA and protein were determined using real-time quantitative reverse transcription PCR （RT-PCR） and flow cytometry analysis, respectively. Results： The expression levels of HLA class I mRNA and proteins were not influenced by age and gender. The relative ratios of HLA class I mRNA were 0.99±0.27 in healthy controls, 0.76±0.19 in benign patients, and 0.48±0.21 in CRC patients. Mean fluorescence intensities of HLA class I were 145.58±38.14 in healthy controls, 102.05±35.98 in benign patients and 87.44±34.01 in CRC patients. HLA class I on PBMCs was significantly down-regulated at both mRNA and protein levels in patients with stage III and IV CRC. CRC patients with lymph node metastasis also showed a decreased HLA class I expression at protein level. Conclusion： HLA class I expressions on PBMCs are associated with staging of CRC and lymph node metastasis. Monitoring the expression of HLA class I on PBMCs may provide useful information for diagnosis and metastasis judgement of CRC.
