Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma

2016 ◽  
Vol 26 (8) ◽  
pp. 1503-1509 ◽  
Author(s):  
Sanne Samuels ◽  
Vivian M. Spaans ◽  
Michelle Osse ◽  
Lex A.W. Peters ◽  
Gemma G. Kenter ◽  
...  

ObjectivesHuman leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial.MethodsThe pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas.ResultsIn squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P< 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months;P= 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months;P= 0.002).ConclusionsUpregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.

2000 ◽  
Vol 85 (3) ◽  
pp. 1176-1179 ◽  
Author(s):  
Yoshikuni Sawai ◽  
Leslie J. DeGroot

Abstract Abstract There are many reports that Graves’ disease (GD) is associated with certain human leukocyte antigen (HLA) molecules, in particular DR3. Here we examined the characteristics of binding of human TSH receptor (TSHR) peptides to this disease-associated HLA class II molecule. DR3 molecules bind TSHR immuonodominant peptide epitopes with intermediate affinity. On the contrary, DR3 binds nonimmunogenic peptides either with poor affinity or not at all, with one exceptional peptide that has extremely high affinity. These results suggest that susceptibility to GD associated with inheritance of a specific HLA class II gene is due to the influence of the HLA molecule-TSHR peptide complex on the T cell repertoire.


2005 ◽  
Vol 12 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Ayesha A. Motala ◽  
Marc Busson ◽  
Einas M. Al-Harbi ◽  
Manal A. A. Khuzam ◽  
Emtiaz M. D. Al-Omari ◽  
...  

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.


1998 ◽  
Vol 66 (6) ◽  
pp. 2022-2026 ◽  
Author(s):  
Franciska M.E Hoekstra ◽  
Marian Witvliet ◽  
Christiaan Y Knoop ◽  
Claes Wassenaar ◽  
Ad J.J.C Bogers ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lik-Chin Ten ◽  
Yoon-Ming Chin ◽  
Mei-Chee Tai ◽  
Edmund Fui-Min Chin ◽  
Yat-Yuen Lim ◽  
...  

2020 ◽  
Vol 4 (4) ◽  
pp. 12-23 ◽  
Author(s):  
Spyros Charonis ◽  
Effie-Photini Tsilibary ◽  
Apostolos Georgopoulos

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4+ T cell activation by the antigen-HLA molecule complex.


2019 ◽  
Vol 294 (52) ◽  
pp. 20246-20258 ◽  
Author(s):  
Bruce J. MacLachlan ◽  
Garry Dolton ◽  
Athanasios Papakyriakou ◽  
Alexander Greenshields-Watson ◽  
Georgina H. Mason ◽  
...  

2009 ◽  
Vol 16 (8) ◽  
pp. 1146-1150 ◽  
Author(s):  
Mouna Stayoussef ◽  
Jihen Benmansour ◽  
Abdul-Qader Al-Irhayim ◽  
Hichem B. Said ◽  
Chiheb B. Rayana ◽  
...  

ABSTRACT Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility to type 1 diabetes (T1D), and susceptible alleles and haplotypes were implicated in the pathogenesis of T1D. This study investigated the heterogeneity in HLA class II haplotype distribution among Tunisian patients with T1D. This was a retrospective case control study done in Monastir in central Tunisia. The subjects comprised 88 T1D patients and 112 healthy controls. HLA-DRB1 and -DQB1 genotyping was done by PCR-sequence-specific priming. Significant DRB1 and DQB1 allelic differences were seen between T1D patients and controls; these differences comprised DRB1*030101 and DQB1*0302, which were higher in T1D patients than in control subjects, and DRB1*070101, DRB1*110101, DQB1*030101, and DQB1*060101, which were lower in T1D patients than in control subjects. In addition, the frequencies of DRB1*030101-DQB1*0201 and DRB1*040101-DQB1*0302 were higher in T1D patients than in control subjects, and the frequencies of DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 haplotypes were lower in T1D patients than in control subjects. Multiple logistic regression analysis revealed the positive association of DRB1*030101-DQB1*0201 and DRB1*040101-DQB1*0302 and the negative association of only DRB1*070101-DQB1*0201 haplotypes with T1D. Furthermore, a significantly increased prevalence of DRB1*030101-DQB1*0201 homozygotes was seen for T1D subjects than for control subjects. Our results confirm the association of specific HLA-DR and -DQ alleles and haplotypes with T1D in Tunisians. The identification of similar and unique haplotypes in Tunisians compared to other Caucasians highlights the need for evaluating the contribution of HLA class II to the genetic susceptibility to T1D with regard to haplotype usage and also to ethnic origin and racial background.


2020 ◽  
Author(s):  
Yu Liu ◽  
Liping Zhang ◽  
Wei Zhang ◽  
Shengyu Wu ◽  
Bin Chen ◽  
...  

Abstract Background Human leukocyte antigen class II (HLA class II) is considered to be related to antitumor immunity. But its value in SCLC is still unclear. In this study, we analyzed HLA class II, programmed death receptor-1/programmed death receptor-1 (PD-1/PD-L1), and immune cells (CD3, CD4, CD8, FOXP3) expression and their role in predicting the patient’s prognosis in SCLC. Methods We analyzed 102 surgical SCLC tumor samples from Shanghai Pulmonary Hospital, China. HLA class II was detected by immunohistochemistry (IHC), and we analyzed the status of HLA class II protein expressed in SCLC. Correlation between HLA class II and PD-1/PD-L1, immune cells, clinicopathological variables, and the survival data were also studied. Results 44.1% of patients expressed HLA class II on tumor-infiltrating lymphocytes (TILs) positively, yet only 5.9% of patients expressed it on SCLC tumor cells. HLA class II on TILs was positively related to PD-1, PD-L1 on TILs, and immune cells. On tumor cells, it also had a positive relationship with PD-1 on TILs (correction coefficient = 0.723, p = 0.006). Comparison of logistic regression models indicates that the odds ratios (ORs) for expression of HLA II on TILs were 3.233 (95% CI: 1.051 ~ 9.95, p = 0.041) when negative for PD-L1 on TILs were compared with those positive for PD-L1 on TILs, and 0.314 (95% CI: 0.118 ~ 0.838, p = 0.021) when negative lymph node metastasis was compared with that positive one. With the Cox regression model, the stage, HLA class II on TILs, PD-L1 on TILs, CD3, CD4, CD8, FOXP3 were considered as protective factors for relapse-free survival (RFS). HLA class II positive patients had a longer RFS (1.20 years, 95% CI: 0.83 ~ 1.57 versus. 3.40 years, 95% CI: 2.47 ~ 4.33, p = 0.015). The high level of HLA class II expressed on TILs was related to a better prognosis. The RFS of patients with positive HLA class II, PD-1/PD-L1, and immune cells was higher than that of these all negative patients (3.45 years, 95% CI: 2.92 ~ 3.97 versus. 2.02 years, 95% CI: 1.32 ~ 2.72, p = 0.001). Conclusions HLA class II was expressed on SCLC TILs, which was correlated with PD-1/PD-L1 and immune cells expression. HLA class II positive patient had a better prognosis.


Sign in / Sign up

Export Citation Format

Share Document