免疫细胞与突发性聋的关系:孟德尔随机化研究

The relationship between immune cells and sudden sensorineural hearing loss:a mendelian randomization study

任银先;于亚峰;肖芝

1:苏州大学附属第一医院耳鼻咽喉科

2:昆山中医医院耳鼻咽喉科

摘要
目的 使用孟德尔随机化(mendelian randomization, MR)来探索免疫细胞表型与突发性聋(sudden sensorineural hearing loss, SSNHL)之间的关系。方法 使用在线的全基因组关联研究(genome-wide association study, GWAS)数据库中的731种免疫表型和SSNHL的GWAS数据进行两样本MR研究。逆方差加权(inverse-variance weighted, IVW)作为主要分析方法,与免疫表型相关的单核苷酸多态性(single nucleotide polymorphism, SNP)作为暴露因素。使用敏感性分析校正来检验MR假设。通过反向MR验证免疫细胞表型和SSNHL之间反向因果关系的可能性。结果 本研究共确定了34种免疫细胞表型与SSNHL的因果关系,包括B细胞组12种,调节性T细胞(Treg)组6种,T细胞、B细胞和自然杀伤细胞(TBNK)组7种,成熟阶段的T细胞组3种,骨髓细胞组5种和常规树突状细胞(conventional dendritic cells, CDC)组1种。有22种表型与SSNHL的患病风险呈负相关,其余12种表型则与SSNHL的患病风险呈正相关。反向MR表明SSNHL与这34种免疫表型之间没有因果关联。结论 本研究从遗传学角度表明免疫细胞表型和突发性聋的发生发展密切相关。
关键词
突发性聋;免疫细胞表型;孟德尔随机化研究
基金项目(Foundation):
作者
任银先;于亚峰;肖芝
参考文献

[1] 刘丹,单春光,张玉波.突发性聋病因学研究进展[J].听力学及言语疾病杂志,2019,27(6):677-680.

[2] ZHANG X,WANG Y,YAN Q,et al.Prognostic correlation of immune-inflammatory markers in sudden sensorineural hearing loss:a retrospective study[J].2023:01455613231202498.DOI:10.1177/0145561323120249

[3] BARADARANFAR M,DADGARNIA M,ZAND V,et al.The Role of immunological factors on sudden sensoryneural hearing loss[J].Iran J Otorhinolaryngol,2018,30(99):219-223.

[4] PAWLAK-OSINSKA K,GOLDA R,OSINSKI S,et al.Circulating immune complexes and heat shock protein 70 in the sera of patients with sudden sensorineural hearing loss[J].The Journal of International Advanced Otology,2019,14(3):426-431.

[5] 孙彩波,孙茂钢,李腾,等.不同方式局部应用糖皮质激素初始治疗突发性聋临床疗效的Meta分析[J].听力学及言语疾病杂志,2020,28(4):432-435.

[6] RICHMOND R C,SMITH G D.Mendelian randomization:concepts and scope[J].Cold Spring Harbor Perspectives in Medicine,2022,12(1):a040501.DOI:10.1101/cshperspect.a040501

[7] THANASSOULIS G,O’DONNELL C J.Mendelian randomization:nature’s randomized trial in the post-genome era[J].Jama,2009,301(22):2386-2388.

[8] LAWLOR D A,TIMPSON N,DAVEY SMITH G,et al.Comments on “mendelian randomization:using genes as instruments for making causal inference in epidemiology”:authors’ response[J].Statistics in Medicine,2008,27(15):2976-2978.

[9] ORR?? V,STERI M,SIDORE C,et al.Complex genetic signatures in immune cells underlie autoimmunity and inform therapy[J].Nature genetics,2020,52(10):1036-1045.

[10] BURGESS S,DUDBRIDGE F,THOMPSON S G.Combining information on multiple instrumental variables in mendelian randomization:comparison of allele score and summarized data methods[J].Statistics in Medicine,2016,35(11):1880-1906.

[11] LIU W,MOLNAR M,GARNHAM C,et al.Macrophages in the human cochlea:saviors or predators—a study using super-resolution immunohistochemistry[J].Frontiers in Immunology,2018,9:223.DOI:10.3389/fimmu.2018.00223

[12] CHEN L,ZHANG G,ZHANG Z,et al.Neutrophil-to-lymphocyte ratio predicts diagnosis and prognosis of idiopathic sudden sensorineural hearing loss:a systematic review and meta-analysis[J].Medicine,2018,97(38):e12492.DOI:10.1097/MD.0000000000012492

[13] YAO Y,GUO Q,LUO W,et al.Inflammatory indicators in peripheral blood in sudden sensorineural hearing loss patients with different audiogram shapes[J].Ear,Nose & Throat Journal,2023,102(2):90-95.

[14] LIU W,DANCKWARDT-LILLIESTR??M N,SCHROTT-FISCHER A,et al.Distribution of immune cells including macrophages in the human cochlea[J].Frontiers in Neurology,2021,12:781702.DOI:10.3389/fneur.2021.781702

[15] YOON S,KIM M,KIM H,et al.Inflammatory cytokines and mononuclear cells in sudden sensorineural hearing loss[J].The Journal of Laryngology & Otology,2019,133(2):95-101.

[16] YAMADA S,KITA J,SHINMURA D,et al.Update on findings about sudden sensorineural hearing loss and insight into its pathogenesis[J].Journal of Clinical Medicine,2022,11(21):6387.DOI:10.3390/jcm11216387

[17] MANTOVANI A,DINARELLO C A,MOLGORA M,et al.IL-1 and related cytokines in innate and adaptive immunity in health and disease[J].Immunity,2019,50(4):778.DOI:10.3389/fimmu.2018.00223

[18] CAVALLI G,COLAFRANCESCO S,EMMI G,et al.Interleukin 1α:a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases[J].Autoimmunity Reviews,2021,20(3):102763.DOI:10.1016/j.autrev.2021.102763

[19] JANG D I,LEE A H,SHIN H Y,et al.The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics[J].International Journal of Molecular Sciences,2021,22(5):2719.DOI:10.3390/ijms22052719

[20] FROSOLINI A,FRANZ L,DALOISO A,et al.Digging into the role of inflammatory biomarkers in sudden sensorineural hearing loss diagnosis and prognosis:a systematic review and meta-analysis[J].Medicina,2022,58(7):963.DOI:10.3390/medicina58070963

[21] MOGHADAM Y J,ASADI M R,ABBASZADEH V,et al.Analysis of NFKB1 and NFKB2 gene expression in the blood of patients with sudden sensorineural hearing loss[J].International Journal of Pediatric Otorhinolaryngology,2023,166:111470.DOI:10.1016/j.ijporl.2023.111470

[22] LI G,YOU D,MA J,et al.The role of autoimmunity in the pathogenesis of sudden sensorineural hearing loss[J].Neural Plasticity,2018,2018(1):7691473.DOI:10.1155/2018/7691473

[23] AL-AZZAWI A,STAPLETON E.Blood tests as biomarkers for the diagnosis and prognosis of sudden sensorineural hearing loss in adults:a systematic review[J].The Journal of Laryngology & Otology,2023,137(9):977-984.

[24] HERRERO-CERVERA A,SOEHNLEIN O,KENNE E.Neutrophils in chronic inflammatory diseases[J].Cellular & Molecular Immunology,2022,19(2):177-191.

[25] KASSNER S S,SCH??TTLER S,BONATERRA G A,et al.Proinflammatory and proadhesive activation of lymphocytes and macrophages in sudden sensorineural hearing loss[J].Audiology and Neurotology,2011,16(4):254-262.

[26] SHETH S,MUKHERJEA D,RYBAK L P,et al.The contribution of anti-oxidant and anti-inflammatory functions of adenosine A1 receptor in mediating otoprotection[J].Inflammatory Mechanisms in Mediating Hearing Loss,2018:149-164.DOI:10.1007/978-3-319-92507-3_8

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