scholarly journals Human Leukocyte Antigen Homozygosity Contributes to Sensitization in Kidney Transplant Candidates

Author(s):  
Joshua Rushakoff ◽  
Loren Gragert ◽  
Marcelo Pando ◽  
Darren Stewart ◽  
Edmung Huang ◽  
...  

Background: Homozygosity for human leukocyte antigens (HLA) has been associated with adverse outcomes after viral infection as well as pregnancy-induced HLA sensitization. We sought to assess the relationship between HLA locus homozygosity and the level of HLA antibody sensitization. Methods: We measured sensitization using the calculated panel reactive antibody (CPRA) value for a large cohort of 147,461 patients added to the US OPTN/UNOS kidney transplant waitlist between December 2014 and December 2019. We used multinomial logistic modeling to compare 62,510 sensitized patients to 84,955 unsensitized controls. Results: We found that the number of homozygous HLA loci was strongly associated with the level of sensitization. Within highly- or extremely-sensitized candidates, women displayed a higher relative abundance of HLA homozygosity at multiple HLA loci as compared to men, with attenuation of this effect in Black candidates. In multinomial logistic modeling, the number of homozygous HLA loci was an independent predictor of sensitization and interacted with female sex but not with other factors associated with sensitization. Conclusions: This study shows that HLA homozygosity is an innate genetic factor that contributes to HLA sensitization, and enhances the effect of pregnancy-related sensitization.

2010 ◽  
Vol 10 (4) ◽  
pp. 282-286 ◽  
Author(s):  
Erkan Yılmaz ◽  
Arman Çekmen ◽  
Emre Akkuş ◽  
Bülent Önal ◽  
Ali Uğur Özalp ◽  
...  

Etiologies of Renal Cell Carcinoma (RCC) are not clear despite of the fact that many risk factors have been suggested. Especially in high stages RCC can affect the immune system in various ways. Human Leukocyte Antigens (HLA) may play a complementary role in the activation between the tumor and immunity. Our aim was to determine the existence of the relationship between HLA system and RCC. By using the standard microlymphocytotoxic method of Terasaki in our study, the HLA A, B, DR and DQ antigen types of 20 patients with RCC Stage Ti and T2 were compared with the control group consisting of healthy 30 people. In our RCC patient group, HLA-A23(9) and DQ7(3) antigens were significantly higher than the control group statistically (p=0.005, p=0.0028; respectively). HLA-A10, DQi, DR10 and B44 antigens were significantly higher in the control group than the patient group (p=0.011; for all). The findings made us suggest that the people, carrying the antigens which were detected in the patient group, were at high risk for RCC and the people, carrying the protective antigens that were detected in the control group were at less risk for RCC. There may be a dramatic regression for the patients who underwent immunotherapy and HLA expression, which is known to play role in tumor biology, may direct the effects of immunotherapeutic agents. Immunologic description and destruction is avoided in case of change or disappearance of HLA expression by cancer cells. Further investigations which will be performed in our population in the future will be more illuminating to confirm those results. We have concluded that, HLA profiles may be evaluated for detection the people at risk of RCC, the prognosis of the patients and their treatments.


2020 ◽  
Vol 9 (12) ◽  
pp. 3986
Author(s):  
Sinem Ünlü ◽  
Nils Lachmann ◽  
Maximilian Jara ◽  
Paul Viktor Ritschl ◽  
Leke Wiering ◽  
...  

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.


2011 ◽  
Vol 25 (4) ◽  
pp. 653-659 ◽  
Author(s):  
Hassan N. Ibrahim ◽  
Melissa A. Skeans ◽  
Qi Li ◽  
Areef Ishani ◽  
Jon J. Snyder

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 847 ◽  
Author(s):  
Hana Rohn ◽  
Rafael Tomoya Michita ◽  
Sabine Schramm ◽  
Sebastian Dolff ◽  
Anja Gäckler ◽  
...  

Human leukocyte antigen (HLA)-E is important for the regulation of anti-viral immunity. BK polyomavirus (BKPyV) reactivation after kidney transplant is a serious complication that can result in BKPyV-associated nephropathy (PyVAN) and subsequent allograft loss. To elucidate whether HLA-E polymorphisms influence BKPyV replication and nephropathy, we determined the HLA-E genotype of 278 living donor and recipient pairs. A total of 44 recipients suffered from BKPyV replication, and 11 of these developed PyVAN. Homozygosity of the recipients for the HLA-E*01:01 genotype was associated with the protection against PyVAN after transplant (p = 0.025, OR 0.09, CI [95%] 0.83–4.89). Considering the time course of the occurrence of nephropathy, recipients with PyVAN were more likely to carry the HLA-E*01:03 allelic variant than those without PyVAN (Kaplan–Meier analysis p = 0.03; OR = 4.25; CI (95%) 1.11–16.23). Our findings suggest that a predisposition based on a defined HLA-E genotype is associated with an increased susceptibility to develop PyVAN. Thus, assessing HLA-E polymorphisms may enable physicians to identify patients being at an increased risk of this viral complication.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Lin Cheng ◽  
Yan Guo ◽  
Shipeng Zhan ◽  
Peiyuan Xia

Objective. We aimed to derive a more precise estimation of the associations between human leukocyte antigens DP (HLA-DP) gene polymorphisms and cervical cancer risk by meta-analysis. Methods. PubMed, EMBASE, ScienceDirect, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were systematically searched to identify studies investigating the relationship between HLA-DP gene polymorphisms and cervical cancer. The associations between them were evaluated by pooled OR and 95% CI. Results. A total of 11 studies including 5008 cases and 9322 controls with 11 HLA-DP alleles were included in the current meta-analysis. Results. The results showed that HLA-DPB1⁎03:01 was significantly associated with an increased risk of cervical cancer (OR=1.252, 95%CI: 1.116-1.403, Pz=0.001), while HLA-DPB1⁎04:02 and HLA-DP rs3117027 G allele were significantly associated with a decreased risk of cervical cancer (OR=0.744, 95%CI: 0.652-0.848, Pz=0.001; OR=0.790, 95%CI: 0.745-0.837, Pz=0.001), and HLA-DP rs9277535 G allele was significantly associated with a decreased risk of cervical cancer in Asia (OR=0.802, 95%CI: 0.753-0.855, Pz=0.001). Subgroup analyses based on race system showed that HLA-DPB1⁎13:01 was significantly associated with an increased risk of cervical cancer in Asia (OR=1.834, 95%CI: 1.107-3.039, Pz=0.019). No significant association was established for the HLA-DP following alleles: DPB1⁎02:01, DPB1⁎02:02, DPB1⁎04:01, DPB1⁎05:01, rs4282438, and rs3077. Conclusion. HLA-DP gene polymorphisms (HLA-DPB1⁎03:01, DPB1⁎04:02, DPB1⁎13:01, rs9277535, and rs3117027) were significantly associated with cervical cancer.


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