AIM: To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease. METHODS: HLA DQ2/8 status was assessed in...AIM: To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease. METHODS: HLA DQ2/8 status was assessed in 443 patients from three ambulatory gastroenterology clinics in Southern Italy (University of Federico Ⅱ, Naples, Loreto Crispi Hospital, Ruggi D'Aragona Hospital, Salerno). Patients were grouped based on disease status [pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)] and DQ2/8 alleles, which correspond to a celiac disease genetic risk gradient. Subject allele frequencies were compared to healthy Italian controls. RESULTS: One hundred and ninety-six out of four hundred and forty-three (44.2%) subjects, median age 56 years and 42.6% female, were DQ2/8 positive. When stratifying by disease we found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Furthermore, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Compared to healthy controls those with functional upper GI diseases disorders had a 1.8 times higher odds of DQ2/8 positivity. Those with liver disease had 1.3 times the odds, albeit not statistically significant, ofDQ2/8 positivity. Both those with IBS and IBD had a lower odds of DQ2/8 positivity compared to healthy controls. CONCLUSION: The proportion of individuals HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD as compared to general population estimates.展开更多
Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus ha...Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.展开更多
Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated ...Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated antigen （MAGE）-A1, MAGE-A3, or synovial sarcoma X-2 （SSX-2） in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen （HLA）-A types were analyzed to provide evidence of designing novel therapy. Methods： Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman＇s rank correlation was used to analyze the relationship of T cell responses. Results： HLA-A＊02：01, A＊02：07, and A＊24：02 were the three most frequent alleles （18.9%, 12.3%, and 11.5%, respectively） among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A＊02：01 and A＊24：02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion： MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.展开更多
Virus-specific CD8+ T cells are thought to be the major anti-viral effector cells in hepatitis C virus (HCV) infection. Indeed, viral clearance is associated with vigorous CD8+ T cell responses targeting multiple epit...Virus-specific CD8+ T cells are thought to be the major anti-viral effector cells in hepatitis C virus (HCV) infection. Indeed, viral clearance is associated with vigorous CD8+ T cell responses targeting multiple epitopes. In the chronic phase of infection, HCV-specific CD8+ T cell responses are usually weak, narrowly focused and display often functional defects regarding cytotoxicity, cytokine production, and proliferative capacity. In the last few years, different mechanisms which might contribute to the failure of HCV-specific CD8+ T cells in chronic infection have been identified, including insufficient CD4+ help, deficient CD8+ T cell differentiation, viral escape mutations, suppression by viral factors, inhibitory cytokines, inhibitory ligands, and regulatory T cells. In addition, host genetic factors such as the host’s human leukocyte antigen (HLA) background may play an important role in the efficiency of the HCV- specific CD8+ T cell response and thus outcome of infection. The growing understanding of the mechanisms contributing to T cell failure and persistence of HCV infection will contribute to the development of successful immunotherapeutical and -prophylactical strategies.展开更多
免疫检查点阻断疗法的出现标志着肿瘤治疗进入新时代, 部分患者因此获益。近年来, 自然杀伤细胞受体家族成员2A(natural killer group 2 member A, NKG2A )和人类白细胞抗原E(human leukocyte antigen E, HLA-E )作为新的免疫检查点受...免疫检查点阻断疗法的出现标志着肿瘤治疗进入新时代, 部分患者因此获益。近年来, 自然杀伤细胞受体家族成员2A(natural killer group 2 member A, NKG2A )和人类白细胞抗原E(human leukocyte antigen E, HLA-E )作为新的免疫检查点受到广泛关注, 且与多种肿瘤细胞的免疫逃逸有关。NKG2A主要表达于大部分自然杀伤(natural killer, NK)细胞表面并在CD8^(+)T细胞上选择性表达。其配体HLA-E在多种肿瘤细胞中表达增强。目前, 部分研究显示, NKG2A抑制剂参与的肿瘤联合免疫治疗可以明显提高肿瘤患者对免疫治疗的总体反应率。因此, NKG2A有望成为肿瘤免疫检查点治疗的新靶点, 为肿瘤患者提供治疗新策略。展开更多
文摘AIM: To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease. METHODS: HLA DQ2/8 status was assessed in 443 patients from three ambulatory gastroenterology clinics in Southern Italy (University of Federico Ⅱ, Naples, Loreto Crispi Hospital, Ruggi D'Aragona Hospital, Salerno). Patients were grouped based on disease status [pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)] and DQ2/8 alleles, which correspond to a celiac disease genetic risk gradient. Subject allele frequencies were compared to healthy Italian controls. RESULTS: One hundred and ninety-six out of four hundred and forty-three (44.2%) subjects, median age 56 years and 42.6% female, were DQ2/8 positive. When stratifying by disease we found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Furthermore, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Compared to healthy controls those with functional upper GI diseases disorders had a 1.8 times higher odds of DQ2/8 positivity. Those with liver disease had 1.3 times the odds, albeit not statistically significant, ofDQ2/8 positivity. Both those with IBS and IBD had a lower odds of DQ2/8 positivity compared to healthy controls. CONCLUSION: The proportion of individuals HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD as compared to general population estimates.
文摘Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.
文摘Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated antigen （MAGE）-A1, MAGE-A3, or synovial sarcoma X-2 （SSX-2） in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen （HLA）-A types were analyzed to provide evidence of designing novel therapy. Methods： Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman＇s rank correlation was used to analyze the relationship of T cell responses. Results： HLA-A＊02：01, A＊02：07, and A＊24：02 were the three most frequent alleles （18.9%, 12.3%, and 11.5%, respectively） among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A＊02：01 and A＊24：02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion： MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.
基金the Deutsche Forschungsgemeinschaft (Emmy Noether Programm, SFB 610)the Wilhelm Sander Stiftung, and the Bundesministerium fuer Wissenschaft und Forschung (Start-up fonds Kompetenznetz Hepatitis)
文摘Virus-specific CD8+ T cells are thought to be the major anti-viral effector cells in hepatitis C virus (HCV) infection. Indeed, viral clearance is associated with vigorous CD8+ T cell responses targeting multiple epitopes. In the chronic phase of infection, HCV-specific CD8+ T cell responses are usually weak, narrowly focused and display often functional defects regarding cytotoxicity, cytokine production, and proliferative capacity. In the last few years, different mechanisms which might contribute to the failure of HCV-specific CD8+ T cells in chronic infection have been identified, including insufficient CD4+ help, deficient CD8+ T cell differentiation, viral escape mutations, suppression by viral factors, inhibitory cytokines, inhibitory ligands, and regulatory T cells. In addition, host genetic factors such as the host’s human leukocyte antigen (HLA) background may play an important role in the efficiency of the HCV- specific CD8+ T cell response and thus outcome of infection. The growing understanding of the mechanisms contributing to T cell failure and persistence of HCV infection will contribute to the development of successful immunotherapeutical and -prophylactical strategies.
