Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression.
Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression.
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DOI：
10.1038/gene.2013.64
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发表时间：
2014-03
影响因子：
5
通讯作者：
Skibola CF
中科院分区：
文献类型：
--
作者：
Sillé FC;Conde L;Zhang J;Akers NK;Sanchez S;Maltbaek J;Riby JE;Smith MT;Skibola CF
人类白细胞抗原（HLA）I类和II类区域的多个滤泡性淋巴瘤（FL）易感性单核苷酸多态性已被鉴定，包括rs6457327、rs3117222、rs2647012、rs10484561、rs9268853和rs2621416。在这里，我们通过实时逆转录定量 PCR 验证了先前的表达数量性状位点结果，并使用流式细胞术、基于细胞的酶联免疫吸附测定和蛋白质印迹研究了 B 淋巴母细胞系和原代树突细胞中的蛋白质表达。我们证实，FL 保护性 rs2647012 连锁变体与扩展单倍型 DRB1*15:01-DQA1*01:02-DQB1*06:02 处于高度连锁不平衡，与 HLA-DQB1 表达增加相关。这种关联在蛋白质水平上仍然显着，并且在不同细胞类型中可重现。我们还发现 HLA-DQB1 表达的差异与激活标记或 II 类、主要组织相容性复合物、反式激活蛋白表达的变化无关，这表明存在替代调节机制的作用。然而，使用 Regulome DB 进行的功能分析并未揭示任何相关的监管候选者。未来的研究应重点关注 HLA-DQB1 蛋白表达增加的临床相关性，通过增加免疫监视促进肿瘤细胞去除。
Multiple follicular lymphoma (FL) susceptibility single-nucleotide polymorphisms in the human leukocyte antigen (HLA) class I and II regions have been identified, including rs6457327, rs3117222, rs2647012, rs10484561, rs9268853 and rs2621416. Here we validated previous expression quantitative trait loci results with real-time reverse transcription quantitative PCR and investigated protein expression in B-lymphoblastoid cell lines and primary dendritic cells using flow cytometry, cell-based enzyme-linked immunosorbent assay and western blotting. We confirmed that FL-protective rs2647012-linked variants, in high linkage disequilibrium with the extended haplotype DRB1*15:01-DQA1*01:02-DQB1*06:02, correlate with increased HLA-DQB1 expression. This association remained significant at the protein level and was reproducible across different cell types. We also found that differences in HLA-DQB1 expression were not related to changes in activation markers or class II, major histocompatibility complex, transactivator expression, suggesting the role of an alternative regulatory mechanism. However, functional analysis using Regulome DB did not reveal any relevant regulatory candidates. Future studies should focus on the clinical relevance of increased HLA-DQB1 protein expression facilitating tumor cell removal through increased immune surveillance.
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影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
30.8
作者：
Fairfax, Benjamin P.;Makino, Seiko;Radhakrishnan, Jayachandran;Plant, Katharine;Leslie, Stephen;Dilthey, Alexander;Ellis, Peter;Langford, Cordelia;Vannberg, Fredrik O.;Knight, Julian C.
通讯作者：
Knight, Julian C.
影响因子：
3.7
作者：
Alcina A;Abad-Grau Mdel M;Fedetz M;Izquierdo G;Lucas M;Fernández O;Ndagire D;Catalá-Rabasa A;Ruiz A;Gayán J;Delgado C;Arnal C;Matesanz F
通讯作者：
Matesanz F
影响因子：
4.5
作者：
Smedby KE;Foo JN;Skibola CF;Darabi H;Conde L;Hjalgrim H;Kumar V;Chang ET;Rothman N;Cerhan JR;Brooks-Wilson AR;Rehnberg E;Irwan ID;Ryder LP;Brown PN;Bracci PM;Agana L;Riby J;Cozen W;Davis S;Hartge P;Morton LM;Severson RK;Wang SS;Slager SL;Fredericksen ZS;Novak AJ;Kay NE;Habermann TM;Armstrong B;Kricker A;Milliken S;Purdue MP;Vajdic CM;Boyle P;Lan Q;Zahm SH;Zhang Y;Zheng T;Leach S;Spinelli JJ;Smith MT;Chanock SJ;Padyukov L;Alfredsson L;Klareskog L;Glimelius B;Melbye M;Liu ET;Adami HO;Humphreys K;Liu J
通讯作者：
Liu J
影响因子：
2.6
作者：
Akers NK;Curry JD;Conde L;Bracci PM;Smith MT;Skibola CF
通讯作者：
Skibola CF