Response to hepatitis B vaccination is co-determined by HLA-DPA1 and -DPB1

Wang, Li-Yu; Chen, Chuen‐Fei; Wu, Tsan-Ming; Lai, Shiau Ting; Chu, Chen‐Chung; Lin, Hans Hsienhong

doi:10.1016/j.vaccine.2019.09.001

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…The antigen-binding affinity of HLA class II molecular variations has also been associated with responsiveness to the HBV vaccine and may share a similar mechanism with the HBV infection (22,24,31,34). In the Taiwan Biobank study, HLA-DPA1*02 and HLA-DPB1*05, which have relatively low-affinity binding to peptide epitopes derived from the HBV nucleocapsid protein, were associated with chronic HBV (31), similar to our HBV nonresponse.…”

Section: Discussionsupporting

confidence: 78%

“…Further large-scale studies are required to provide more concrete data. Nevertheless, the results of this study may be incorporated into other research to broaden the understanding of the immune response of the HBV vaccine among young Taiwanese adults (24,34,40). Third, as a result of limited funding, we did not test HLA-DR, despite extensive studies both domestically and internationally (20,23,(26)(27)(28)(29) reporting a strong linkage disequilibrium between HLA-DR and -DQ alleles.…”

Section: Discussionmentioning

confidence: 98%

“…Many studies have also indicated that several HLA alleles are closely linked to the immunological response to the HBVac (21)(22)(23). Hence, HLA is also hypothesized to play a key role in responsiveness to the HBVac (24).…”

Section: Introductionmentioning

confidence: 99%

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Association of HLA-DPA1, HLA-DPB1, and HLA-DQB1 Alleles With the Long-Term and Booster Immune Responses of Young Adults Vaccinated Against the Hepatitis B Virus as Neonates

et al. 2021

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The neonatal hepatitis B vaccination (HBVac) was implemented 35 years ago in Taiwan, but many vaccinees exhibit inadequate long-term vaccine-induced seroprotective hepatitis B surface antibody (anti-HBs) levels. We investigated the association of the human leukocyte antigen (HLA) alleles (DPA1, DPB1, DQA1, and DQB1) with the long-term immunological response to the neonatal HBVac and adolescent booster HBVac in a Taiwanese cohort. We divided 281 Han students (median age 22, age range 17–29 years) into the following groups: (1) Group A (n = 61): anti-HBs titer ≥ 10 mIU/mL at the beginning of the study; (2) Group B (n = 75): anti-HBs level > 1000 mIU/mL after the first booster; (3) Group C (n = 37): anti-HBs level < 10 mIU/mL after the first booster; and (4) Group D (n = 5): anti-HBs level < 10 mIU/mL after three boosters. DQA1, DQB1, DPA1, and DPB1 typing of the participants was performed using sequence-specific oligonucleotides. Associations of HLA alleles and haplotypes with effects on neonatal HBVac and booster HBVac were examined through logistic regression analysis and Fisher’s exact test. A false discovery rate-based measure of significance, the q-value, was used for multiple comparisons, and an association was considered significant if the corresponding q-value was < 0.1. DPA1 alleles were associated with the long-term immunological response to the neonatal HBVac. The estimated odds ratio (OR) of the lack of HBV protective immunity when carrying an additional DPA1*01 and DPA1*02 was 0.36 [95% confidence interval (CI) = 0.17–0.76, p = 0.0076] and 2.39 (95% CI = 1.17–4.87, p = 0.016), respectively. DPB1 and DQB1 alleles were associated with a response to the adolescent booster vaccination. The estimated ORs of being nonresponsive to the first booster when carrying an additional DPB1*05 and DQB1*02 were 2.11 (95% CI = 1.13–3.93, p = 0.019) and 3.73 (95% CI = 1.43–9.71, p = 0.0070), respectively. All DPB1*03 carriers responded to the first booster (p of Fisher’s exact test = 0.0045). In our study, we discovered that HLA-DPA1 was primarily associated with the long-term response of primary infantile HBVac, and HLA-DPB1 and HLA-DQB1 exhibited associations with the HBV booster vaccination.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 98%

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Association of HLA-DPA1, HLA-DPB1, and HLA-DQB1 Alleles With the Long-Term and Booster Immune Responses of Young Adults Vaccinated Against the Hepatitis B Virus as Neonates

et al. 2021

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“…Subsequently, the genotypes of DPB1 * 05:01, 09:01, and DPB1 * 02:01, 04:01, and 04:02 were again found to be susceptible to HBV in Japanese [9] and Chinese [10] populations. The studies also found that some DPB1 alleles and rs9277535G related to weak HBV vaccines response [23] , low sensitive of HBV drug therapy [15] , incidence of occult HBV infection [24] , and also prone to hepatocellular carcinoma development [25] . In our study, we found the strongly association between rs9277535 and HLA-DPB1 alleles and HBV infection susceptibility.…”

Section: Discussionmentioning

confidence: 93%

Variation of HLA-DPB1 Gene in Hepatitis B Infection

Liu

et al. 2020

Preprint

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Background: Hepatitis B virus (HBV) affects approximately 68 million people in China. 10-15% of adult infected with HBV will develop to chronic HBV, liver cirrhosis (LC), liver failure and hepatocellular carcinoma (HCC). The human leukocyte antigen HLA-DPB1 gene polymorphism and expression were identified to be associated with HBV susceptible and spontaneous clearance. We evaluated the role of HLA-DPB1 gene polymorphism in HBV infection.Methods: In this study, HLA-DPB1, rs9277535 polymorphisms were investigated in 259 HBV infection patients (CHB) and 442 healthy controls (HC) by using a sequence based typing. The mRNA of HLA-DPB1 were measured by real-time polymerase chain reaction (RT-PCR). Results: The results shown that DPB1 gene, rs9277535 were all associated with HBV infection in the Sichuan Han population. Rs9277535A, DPB1*04:02 play a protected role in HBV infection, Rs9277535G, DPB1*05:01 prone to susceptible to HBV infection. rs9277535GG have significantly higher HLA-DPB1 mRNA expression in HBV group compared that in HC group. DPB1*05:01 and DPB1*21:01 have a significantly lower HLA-DPB1 mRNA expression in HBV infection group compared than HC group. The meta-analysis revealed that HLA-DPB1*02:01, DPB1*02:02, DPB1*04:01 and DPB1*04:02 protected against HBV infection, while DPB1*05:01, DPB1*09:01, and DPB1*13:01 were risk factors for HBV infection susceptibility. DPB1*02:01 and DPB1*04:01 were prone to HBV spontaneous clearance, while DPB1*05:01 and DPB1*13:01 were associated with chronic HBV infection.Conclusions: DPB1 alleles and rs9277535 have a major effect on the risk of HBV infection, HBV infection associated with lower HLA-DPB1 expression. DPB1 alleles have important role in HBV susceptible and spontaneous clearance.

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“…Our results on the function and pathways of critical gene enrichments confirm these mechanisms (Supplementary Table S1). Wang et al, 2019). SLE has been linked to polymorphisms in the HLA-D region that vary by race and geographical region.…”

Section: Disscussionmentioning

confidence: 99%

Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses

Chen

Lan

et al. 2021

Front. Bioeng. Biotechnol.

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Lupus nephritis (LN) is an important driver of end-stage renal disease (ESRD). However, few biomarkers are available for evaluating the diagnosis and prognosis of LN. For this study, we downloaded microarray data of multiple LN expression profiles from the GEO database. We used the WGCNA and R limma packages to identify LN hub genes and differentially-expressed genes (DEGs). We identified nine co-DEGs in the intersection with LN-related genes from the Genecards database. We found DEGs that are primarily associated with immune-related functions and pathways (including with the complement pathway, primary immunodeficiency markers, and MHC-like protein complexes) through our comprehensive GSEA, GO, and KEGG enrichment analyses. We used other LN and SLE validation datasets and discovered six explicitly expressed co-DEGs: HLA-DMA, HLA-DPA1, HLA-DPB1, HLA-DRA, IL10RA, and IRF8 in the LN set; ROC and Precision-Recall curve analyses revealed that these six genes have a good diagnostic efficacy. The correlation analysis with prognostic data from the Nephroseq database indicates that the differential expression of these co-DEGs is associated with a low glomerular filtration rate in that cohort. Additionally, we used a single-cell LN database of immune cells (for the first time) and discovered these co-DEGs to be predominantly distributed in different types of macrophages and B cells. In conclusion, by integrating multiple approaches for DEGs discovery, we identified six valuable biomarkers that are strongly correlated with the diagnosis and prognosis of LN. These markers can help clarify the pathogenesis and improve the clinical management of LN.

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Response to hepatitis B vaccination is co-determined by HLA-DPA1 and -DPB1

Cited by 11 publications

References 24 publications

Association of HLA-DPA1, HLA-DPB1, and HLA-DQB1 Alleles With the Long-Term and Booster Immune Responses of Young Adults Vaccinated Against the Hepatitis B Virus as Neonates

Association of HLA-DPA1, HLA-DPB1, and HLA-DQB1 Alleles With the Long-Term and Booster Immune Responses of Young Adults Vaccinated Against the Hepatitis B Virus as Neonates

Variation of HLA-DPB1 Gene in Hepatitis B Infection

Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses

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