Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression

Sillé, Fenna C.M.; Conde, Lucía; Zhang, J; Akers, Nicholas K.; Sanchez, Sylvia; Maltbaek, Joanna H.; Riby, Jacques; Smith, Martyn T.; Skibola, Christine F.

doi:10.1038/gene.2013.64

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…In silico cis -eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. rs2647012-T is linked to higher expression of HLA-DQB1 , an observation also reported by Sille and colleagues 20 . rs2647012-T is linked with lower expression of HLA-DQA2 , contradicting the protective effect rendered by rs2647012-T. Our results could be important as increased HLA-DQB1 expression may enhance antigen presentation, immune surveillance and the elimination of tumor cells.…”

Section: Discussionsupporting

confidence: 73%

SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression

Ten

Chin

Tai

et al. 2017

Sci Rep

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Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37–0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35–0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.

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Section: Discussionsupporting

confidence: 73%

SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression

Ten

Chin

Tai

et al. 2017

Sci Rep

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“…HLA class I genes including HLA-A, HLA-B , and HLA-C are expressed on the surface of all nucleated cells, whereas the expression of class II genes; HLA-DR, HLA-DQ , and HLA-DP is restricted to professional antigen presenting cells ( 1 , 2 ). Recent studies have reported varying expression levels of HLA alleles based on the quantitative polymerase chain reaction (qPCR) ( 3 – 9 ) and the mean fluorescence intensity (MFI) ( 10 , 11 ). The differential expression of HLA genes and alleles has been associated with immunologically mediated diseases, such as Crohn’s disease ( 7 ) and HIV ( 11 , 12 ), follicular lymphoma ( 9 ), lung cancer ( 13 ), ovarian cancer ( 14 , 15 ), and the outcome of HSCT through the increased risk of graft versus host disease (GvHD) ( 5 , 10 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

HLA RNA Sequencing With Unique Molecular Identifiers Reveals High Allele-Specific Variability in mRNA Expression

et al. 2021

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The HLA gene complex is the most important single genetic factor in susceptibility to most diseases with autoimmune or autoinflammatory origin and in transplantation matching. Most studies have focused on the vast allelic variation in these genes; only a few studies have explored differences in the expression levels of HLA alleles. In this study, we quantified mRNA expression levels of HLA class I and II genes from peripheral blood samples of 50 healthy individuals. The gene- and allele-specific mRNA expression was assessed using unique molecular identifiers, which enabled PCR bias removal and calculation of the number of original mRNA transcripts. We identified differences in mRNA expression between different HLA genes and alleles. Our results suggest that HLA alleles are differentially expressed and these differences in expression levels are quantifiable using RNA sequencing technology. Our method provides novel insights into HLA research, and it can be applied to quantify expression differences of HLA alleles in various tissues and to evaluate the role of this type of variation in transplantation matching and susceptibility to autoimmune diseases.

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“…[1,2] Recently a few studies reported varying expression levels of HLA alleles based on the real-time polymerase chain reaction (PCR) and the mean fluorescence intensity (MFI). [3–10] The differential expression of HLA alleles has been associated with immunologically mediated diseases, such as Crohn’s disease [11] and HIV [6,12], follicular lymphoma[7], and the outcome of HSCT through the risk of graft versus host disease (GvHD)[8,9]. In fact, incompatibilities between the donor and the recipient in HSCT have made the expression differences of HLA molecules an interesting target for finding permissive mismatches.…”

Section: Introductionmentioning

confidence: 99%

HLA RNAseq reveals high allele-specific variability in mRNA expression

Johansson

Koskela

et al. 2018

Preprint

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18The HLA gene complex is the most important, single genetic factor in susceptibility to most 19 diseases with autoimmune or autoinflammatory origin and in transplantation matching. The majority of 20 the studies have focused on the huge allelic variation in these genes; only a few studies have explored 21 differences in expression levels of HLA alleles. To study the expression levels of HLA alleles more 22 systematically we utilised two different RNA sequencing methods. Illumina RNAseq has a high 23 sequencing accuracy and depth but is limited by the short read length, whereas Oxford Nanopore's 24 technology can sequence long templates, but has a poor accuracy. We studied allelic mRNA levels of 25 HLA class I and II alleles from peripheral blood samples of 50 healthy individuals. The results 26 demonstrate large differences in mRNA expression levels between HLA alleles. The method can be 27 applied to quantitate the expression differences of HLA alleles in various tissues and to evaluate the role 28 of this type of variation in transplantation matching and susceptibility to autoimmune diseases. 29 3 30 Author Summary 31 32Even though HLA is widely studied less is known of its allele-specific expression. Due to the pivotal role 33 of HLA in infection response, autoimmunity, and transplantation biology its expression surely must play 34 a part as well. In hematopoietic stem cell transplantation the challenge often is to find a suitable HLA-35 matched donor due to the high allelic variation. Classical HLA typing methods do not take into account 36 HLA allele-specific expression. However, differential allelic expression levels could be crucial in finding 37 permissive mismatches in order to save a patient's life. Additionally, differential HLA expression levels 38 can lead into beneficial impact in viral clearance but also undesirable effects in autoimmune diseases. To 39 study HLA expression we developed a novel RNAseq-based method to systematically characterize allele-40 specific expression levels of classical HLA genes. We tested our method in a set of 50 healthy individuals 41 and found differential expression levels between HLA alleles as well as interindividual variability at the 42 gene level. Since NGS is already well adopted in HLA research the next step could be to determine HLA 43 allele-specific expression in addition to HLA allelic variation and HLA-disease association studies in 44 various cells, tissues, and diseases. 45 54 reaction (PCR) and the mean fluorescence intensity (MFI).[3-10] The differential expression of HLA 55 alleles has been associated with immunologically mediated diseases, such as Crohn's disease [11] and 56 HIV [6,12], follicular lymphoma[7], and the outcome of HSCT through the risk of graft versus host 57 disease (GvHD)[8,9]. In fact, incompatibilities between the donor and the recipient in HSCT have made 58 the expression differences of HLA molecules an interesting target for finding permissive mismatches. 59 Although currently only the qualitative HLA typing is considered in dono...

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Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression

Cited by 10 publications

References 28 publications

SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression

SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression

HLA RNA Sequencing With Unique Molecular Identifiers Reveals High Allele-Specific Variability in mRNA Expression

HLA RNAseq reveals high allele-specific variability in mRNA expression

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