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Statistical genetics and polygenic risk score for precision medicine. 精准医学的统计遗传学和多基因风险评分。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-06-17 DOI: 10.1186/s41232-021-00172-9
Takahiro Konuma, Yukinori Okada

The prediction of disease risks is an essential part of personalized medicine, which includes early disease detection, prevention, and intervention. The polygenic risk score (PRS) has become the standard for quantifying genetic liability in predicting disease risks. PRS utilizes single-nucleotide polymorphisms (SNPs) with genetic risks elucidated by genome-wide association studies (GWASs) and is calculated as weighted sum scores of these SNPs with genetic risks using their effect sizes from GWASs as their weights. The utilities of PRS have been explored in many common diseases, such as cancer, coronary artery disease, obesity, and diabetes, and in various non-disease traits, such as clinical biomarkers. These applications demonstrated that PRS could identify a high-risk subgroup of these diseases as a predictive biomarker and provide information on modifiable risk factors driving health outcomes. On the other hand, there are several limitations to implementing PRSs in clinical practice, such as biased sensitivity for the ethnic background of PRS calculation and geographical differences even in the same population groups. Also, it remains unclear which method is the most suitable for the prediction with high accuracy among numerous PRS methods developed so far. Although further improvements of its comprehensiveness and generalizability will be needed for its clinical implementation in the future, PRS will be a powerful tool for therapeutic interventions and lifestyle recommendations in a wide range of diseases. Thus, it may ultimately improve the health of an entire population in the future.

疾病风险预测是个性化医疗的重要组成部分,包括疾病的早期检测、预防和干预。多基因风险评分(PRS)已成为量化遗传倾向性预测疾病风险的标准。PRS利用全基因组关联研究(GWASs)阐明的具有遗传风险的单核苷酸多态性(snp),并以这些具有遗传风险的snp的加权和得分计算,使用来自GWASs的效应大小作为权重。PRS在许多常见疾病(如癌症、冠状动脉疾病、肥胖和糖尿病)以及各种非疾病特征(如临床生物标志物)中的应用已经得到了探索。这些应用表明,PRS可以识别这些疾病的高风险亚组,作为预测性生物标志物,并提供有关驱动健康结果的可改变风险因素的信息。另一方面,在临床实践中实施PRS存在一些局限性,如计算PRS的种族背景的敏感性存在偏倚,即使在同一人群中也存在地理差异。此外,在目前开发的众多PRS方法中,哪一种方法最适合高精度的预测仍不清楚。尽管在未来的临床应用中需要进一步提高其全面性和普遍性,但PRS将成为广泛疾病的治疗干预和生活方式建议的有力工具。因此,它可能最终在未来改善整个人口的健康。
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引用次数: 18
Updates on genetics in systemic sclerosis. 系统性硬化症遗传学的最新进展。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-06-15 DOI: 10.1186/s41232-021-00167-6
Yuko Ota, Masataka Kuwana

Systemic sclerosis (SSc) is a complex disease, in which an interaction of genetic and environmental factors plays an important role in its development and pathogenesis. A number of genetic studies, including candidate gene analysis and genome-wide association study, have found that the associated genetic variants are mainly localized in noncoding regions in the expression quantitative trait locus and influence corresponding gene expression. The gene variants identified as a risk for SSc susceptibility include those associated with innate immunity, adaptive immune response, and cell death, while there are only few SSc-associated genes involved in the fibrotic process or vascular homeostasis. Human leukocyte antigen class II genes are associated with SSc-related autoantibodies rather than SSc itself. Since the pathways between the associated genotype and phenotype are still poorly understood, further investigations using multi-omics technologies are necessary to characterize the complex molecular architecture of SSc, identify biomarkers useful to predict future outcomes and treatment responses, and discover effective drug targets.

系统性硬化症(SSc)是一种复杂的疾病,遗传和环境因素在其发生和发病过程中起着重要作用。包括候选基因分析和全基因组关联研究在内的许多遗传学研究发现,相关遗传变异主要定位于表达数量性状位点的非编码区域,并影响相应基因的表达。被确定为SSc易感性风险的基因变异包括那些与先天免疫、适应性免疫反应和细胞死亡相关的基因,而只有少数SSc相关基因参与纤维化过程或血管稳态。人白细胞抗原II类基因与SSc相关自身抗体相关,而不是与SSc本身相关。由于相关基因型和表型之间的途径仍然知之甚少,因此有必要使用多组学技术进行进一步的研究,以表征SSc的复杂分子结构,鉴定可用于预测未来结果和治疗反应的生物标志物,并发现有效的药物靶点。
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引用次数: 12
VEGFR1-tyrosine kinase signaling in pulmonary fibrosis. vegfr1 -酪氨酸激酶信号在肺纤维化中的作用。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-06-03 DOI: 10.1186/s41232-021-00166-7
Hideki Amano, Yoshio Matsui, Ko Hatanaka, Kanako Hosono, Yoshiya Ito

Vascular endothelial growth factor (VEGF) is not only an important factor for angiogenesis but also lung development and homeostasis. VEGF-A binds three tyrosine kinase (TK) receptors VEGFR1-3. Idiopathic pulmonary fibrosis (IPF) is one of the poor prognoses of lung diseases. The relationship of VEGF and IPF remains to be clarified. Treatment with nintedanib used for the treatment of IPF reduced fibroblast proliferation, inhibited TK receptors, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and VEGFR. Because the effect of that treatment is still not satisfactory, the emergence of new therapeutic agents is needed. This review describes the enhancement of pulmonary fibrosis by VEGFR1-TK signal and suggests that the blocking of the VEGFR1-TK signal may be useful for the treatment of pulmonary fibrosis.

血管内皮生长因子(Vascular endothelial growth factor, VEGF)不仅是血管生成的重要因子,也是肺发育和体内平衡的重要因子。VEGF-A结合三个酪氨酸激酶(TK)受体VEGFR1-3。特发性肺纤维化(Idiopathic pulmonary fibrosis, IPF)是一种预后不良的肺部疾病。VEGF与IPF的关系尚不明确。用尼达尼布治疗IPF可降低成纤维细胞增殖,抑制TK受体、血小板衍生生长因子受体(PDGFR)、成纤维细胞生长因子受体(FGFR)和VEGFR。由于这种治疗的效果仍然不令人满意,因此需要出现新的治疗药物。本综述描述了VEGFR1-TK信号对肺纤维化的增强作用,并提示阻断VEGFR1-TK信号可能有助于肺纤维化的治疗。
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引用次数: 10
Neurological pathogenesis of SARS-CoV-2 (COVID-19): from virological features to clinical symptoms. SARS-CoV-2(COVID-19)的神经系统发病机制:从病毒学特征到临床症状。
IF 5 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-05-07 DOI: 10.1186/s41232-021-00165-8
Yoshitaka Kase, Hideyuki Okano

Since the worldwide outbreak of coronavirus disease 2019 (COVID-19) in 2020, various research reports and case reports have been published. It has been found that COVID-19 causes not only respiratory disorders but also thrombosis and gastrointestinal disorders, central nervous system (CNS) disorders, and peripheral neuropathy. Compared to other disorders, there are low number of research reports and low number of summaries on COVID-19-related neural disorders. Therefore, focusing on neural disorders, we outline both basic research and clinical manifestations of COVID-19-related neural disorders.

自 2020 年全球爆发冠状病毒病 2019(COVID-19)以来,各种研究报告和病例报告相继发表。研究发现,COVID-19不仅会导致呼吸系统疾病,还会导致血栓和胃肠道疾病、中枢神经系统(CNS)疾病和周围神经病变。与其他疾病相比,COVID-19 相关神经疾病的研究报告和摘要数量较少。因此,我们以神经系统疾病为重点,概述了 COVID-19 相关神经系统疾病的基础研究和临床表现。
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引用次数: 0
Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases. T滤泡调节细胞在自身免疫性疾病中的分化、功能和作用
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-05-03 DOI: 10.1186/s41232-021-00164-9
He Hao, Shingo Nakayamada, Yoshiya Tanaka

T follicular helper cells participate in stimulating germinal center (GC) formation and supporting B cell differentiation and autoantibody production. However, T follicular regulatory (Tfr) cells suppress B cell activation. Since changes in the number and functions of Tfr cells lead to dysregulated GC reaction and autoantibody response, targeting Tfr cells may benefit the treatment of autoimmune diseases. Differentiation of Tfr cells is a multistage and multifactorial process with various positive and negative regulators. Therefore, understanding the signals regulating Tfr cell generation is crucial for the development of targeted therapies. In this review, we discuss recent studies that have elucidated the roles of Tfr cells in autoimmune diseases and investigated the modulators of Tfr cell differentiation. Additionally, potential immunotherapies targeting Tfr cells are highlighted.

T滤泡辅助细胞参与刺激生发中心(GC)的形成,支持B细胞分化和自身抗体的产生。然而,T滤泡调节(Tfr)细胞抑制B细胞的活化。由于Tfr细胞数量和功能的改变导致GC反应和自身抗体反应失调,靶向Tfr细胞可能有利于自身免疫性疾病的治疗。Tfr细胞的分化是一个多阶段、多因子的过程,有多种正、负调节因子。因此,了解调节Tfr细胞生成的信号对于靶向治疗的发展至关重要。在这篇综述中,我们讨论了最近的研究,阐明了Tfr细胞在自身免疫性疾病中的作用,并研究了Tfr细胞分化的调节剂。此外,潜在的针对Tfr细胞的免疫疗法被强调。
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引用次数: 18
Facial nerve regeneration using silicone conduits filled with ammonia-functionalized graphene oxide and frankincense-embedded hydrogel. 用氨功能化氧化石墨烯和乳香水凝胶填充的硅胶导管再生面神经。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-04-26 DOI: 10.1186/s41232-021-00162-x
Sepehr Aghajanian, Aliasghar Taghi Doulabi, Masoume Akhbari, Alireza Shams

Background: Silicone tube (ST) conduits have been accepted as a therapeutic alternative to direct nerve suturing in the treatment of nerve injuries; however, the search for optimal adjuncts to maximize the outcomes is still ongoing. Frankincense (Fr) and graphene oxide (GO) have both been cited as neuroregenerative compounds in the literature. This study assesses the efficacy of these materials using a ST conduit in a rat facial nerve motor neuron axotomy model, distal to the stylomastoid foramen.

Methods: Ammonia-functionalized graphene oxide (NH2-GO) and/or Fr extract were embedded in a collagen-chitosan hydrogel and were injected inside a ST. The ST was inserted in the gap between the axotomized nerve stumps. Return of function in eye closure, blinking reflex, and vibrissae movements were assessed and compared to control groups through 30 days following axotomy. To assess the histological properties of regenerated nerves, biopsies were harvested distal to the axotomy site and were visualized through light and fluorescence microscopy using LFB and anti-MBP marker, respectively.

Results: There was no significant difference in behavioral test results between groups. Histological analysis of the nerve sections revealed increased number of regenerating axons and mean axon diameter in NH2-GO group and decreased myelin surface area in Fr group. Using both NH2-GO and Fr resulted in increased number of regenerated axons and myelin thickness compared to the hydrogel group.

Conclusions: The findings suggest a synergistic effect of the substances above in axon regrowth, notably in myelin regeneration, where Fr supposedly decreases myelin synthesis.

背景:硅胶管(ST)导管在神经损伤的治疗中已被接受为直接神经缝合的替代治疗方法;然而,寻找最佳的辅助药物以最大化结果仍在进行中。乳香(Fr)和氧化石墨烯(GO)在文献中都被引用为神经再生化合物。本研究利用ST导管在大鼠面神经运动神经元轴切模型中评估了这些材料的疗效,该模型位于茎突乳突孔远端。方法:将氨官能化氧化石墨烯(NH2-GO)和/或Fr提取物包埋在胶原-壳聚糖水凝胶中,注射到ST内。ST被插入到神经残端之间的间隙中。闭眼、眨眼反射和触须运动的功能恢复进行评估,并在闭眼后30天与对照组进行比较。为了评估再生神经的组织学特性,在轴切部位远端取活检组织,分别使用LFB和抗mbp标记物在光镜和荧光显微镜下观察。结果:两组患者行为测试结果无显著差异。神经切片组织学分析显示,NH2-GO组再生轴突数量和平均轴突直径增加,Fr组髓鞘表面积减少。与水凝胶组相比,使用NH2-GO和Fr可增加再生轴突的数量和髓鞘厚度。结论:研究结果表明,上述物质在轴突再生中具有协同作用,特别是在髓鞘再生中,Fr可能会减少髓鞘合成。
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引用次数: 3
Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects. 牙髓干细胞细胞外囊泡对大鼠颅骨骨缺损骨再生的影响。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-04-14 DOI: 10.1186/s41232-021-00163-w
Yuka Imanishi, Masaki Hata, Ryohei Matsukawa, Atsushi Aoyagi, Maiko Omi, Makoto Mizutani, Keiko Naruse, Shogo Ozawa, Masaki Honda, Tatsuaki Matsubara, Jun Takebe

Background: Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation.

Methods: DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation.

Results: Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL.

Conclusions: These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.

背景:细胞外囊泡(EVs)是由多种细胞分泌的。特别是间充质干细胞(MSC)衍生的EVs (MSC-EVs)具有组织修复能力和抗炎特性。牙髓干细胞(DPSCs)是一种从牙髓组织中分离出来的间充质干细胞,与其他间充质干细胞相比,对身体的侵袭性较小,可以从年轻人身上采集。在这项研究中,我们研究了由dpsc分泌的EVs (DPSC-EVs)对骨形成的影响。方法:从dpsc细胞培养基中分离dpsc - ev。将DPSC-EVs与胶原(COL)、β-磷酸三钙(β-TCP)或羟基磷灰石(HA)一起单侧注入大鼠颅骨骨缺损。通过显微计算机断层扫描(micro-CT)和组织学观察分析dpsc - ev的作用。结果:Micro-CT显示,将dpsc - ev与上述支架一起使用可使缺损周围骨形成。dpsc - ev /COL特异性地导致缺损中心的骨形成。组织学观察显示DPSC-EVs/COL促进新骨形成。DPSCs - ev /COL对骨缺损部位的影响与DPSCs/COL移植几乎相同。结论:这些结果提示dpsc - ev可能是骨组织再生的有效工具。
{"title":"Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects.","authors":"Yuka Imanishi,&nbsp;Masaki Hata,&nbsp;Ryohei Matsukawa,&nbsp;Atsushi Aoyagi,&nbsp;Maiko Omi,&nbsp;Makoto Mizutani,&nbsp;Keiko Naruse,&nbsp;Shogo Ozawa,&nbsp;Masaki Honda,&nbsp;Tatsuaki Matsubara,&nbsp;Jun Takebe","doi":"10.1186/s41232-021-00163-w","DOIUrl":"https://doi.org/10.1186/s41232-021-00163-w","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation.</p><p><strong>Methods: </strong>DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation.</p><p><strong>Results: </strong>Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL.</p><p><strong>Conclusions: </strong>These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"12"},"PeriodicalIF":8.1,"publicationDate":"2021-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00163-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25591963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Transcriptomic studies of systemic lupus erythematosus. 系统性红斑狼疮的转录组研究。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-04-09 DOI: 10.1186/s41232-021-00161-y
Masahiro Nakano, Yukiko Iwasaki, Keishi Fujio

The management of systemic lupus erythematosus (SLE) remains challenging for clinicians because of the clinical heterogeneity of this disease. In attempts to identify useful biomarkers for the diagnosis of and treatment strategies for SLE, previous microarray and RNA sequencing studies have demonstrated several disease-relevant signatures in SLE. Of these, the interferon (IFN) signature is complex, involving IFNβ- and IFNγ-response genes in addition to IFNα-response genes. Some studies revealed that myeloid lineage/neutrophil and plasma cell signatures as well as the IFN signature were correlated with disease activity, lupus nephritis, and complications of pregnancy, although some of these findings remain controversial. Cell-type-specific gene expression analysis revealed the importance of an exhaustion signature in CD8+ T cells for SLE outcome. Recent single-cell RNA sequencing analyses of SLE blood and tissues demonstrated molecular heterogeneity and identified several distinct subpopulations as key players in SLE pathogenesis. Further studies are required to identify novel treatment targets and determine precise patient stratification in SLE. In this review, we discuss the findings and limitations of SLE transcriptomic studies.

由于系统性红斑狼疮(SLE)的临床异质性,临床医生对该病的治疗仍然面临挑战。为了确定系统性红斑狼疮诊断和治疗策略的有用生物标志物,先前的芯片和 RNA 测序研究已经证明了系统性红斑狼疮的几个疾病相关特征。其中,干扰素(IFN)特征非常复杂,除了IFNα反应基因外,还涉及IFNβ和IFNγ反应基因。一些研究显示,髓系/中性粒细胞和浆细胞特征以及 IFN 特征与疾病活动、狼疮肾炎和妊娠并发症相关,但其中一些研究结果仍存在争议。细胞类型特异性基因表达分析表明,CD8+ T细胞的衰竭特征对系统性红斑狼疮的预后非常重要。最近对系统性红斑狼疮血液和组织进行的单细胞 RNA 测序分析显示了分子异质性,并确定了几个不同的亚群在系统性红斑狼疮发病机制中起着关键作用。要确定新的治疗靶点并对系统性红斑狼疮患者进行精确分层,还需要进一步的研究。在这篇综述中,我们将讨论系统性红斑狼疮转录组研究的发现和局限性。
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引用次数: 0
Frontiers of inflammatory disease research: inflammation in cardiovascular-cerebral diseases. 炎症性疾病研究的前沿:心脑血管疾病中的炎症。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-03-29 DOI: 10.1186/s41232-021-00160-z
Daiju Fukuda, Masataka Sata
{"title":"Frontiers of inflammatory disease research: inflammation in cardiovascular-cerebral diseases.","authors":"Daiju Fukuda,&nbsp;Masataka Sata","doi":"10.1186/s41232-021-00160-z","DOIUrl":"https://doi.org/10.1186/s41232-021-00160-z","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"10"},"PeriodicalIF":8.1,"publicationDate":"2021-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00160-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25528597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Inborn errors of immunity-recent advances in research on the pathogenesis. 先天性免疫缺陷——发病机制研究进展。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2021-03-25 DOI: 10.1186/s41232-021-00159-6
Motoi Yamashita, Kento Inoue, Tsubasa Okano, Tomohiro Morio

Primary immunodeficiency (PID) is a genetic disorder with a defect of one of the important components of our immune system. Classical PID has been recognized as a disorder with loss of function of the immune system. Recent studies have unveiled disorders with immune dysfunction with autoimmunity, autoinflammation, allergy, or predisposition to malignancy. Some of them were caused by an augmented immune function or a defect in immune regulation. With this background, the term inborn errors of immunity (IEI) is now used to refer to PID in the International Union of Immunological Societies (IUIS) classification. More than 400 responsible genes have been identified in patients with IEI so far, and importantly, many of them identified lately were caused by a heterologous mutation. Moreover, the onset is not necessarily in childhood, and we started seeing more and more IEI patients diagnosed in adulthood in the clinical settings. Recent advances in genetic analysis, including whole-exome analysis, whole-genome analysis, and RNA-seq have contributed to the identification of the disease-causing gene mutation. We also started to find heterogeneity of phenotype even in the patients with the same mutation in the same family, leading us to wonder if modifier gene or epigenetic modification is involved in the pathogenesis. In contrast, we accumulated many cases suggesting genetic heterogeneity is associated with phenotypic homogeneity. It has thus become difficult to deduce a responsible gene only from the phenotype in a certain type of IEI. Current curative therapy for IEI includes hematopoietic cell transplantation and gene therapy. Other curative therapeutic modalities have been long waited and are to be introduced in the future. These include a small molecule that inhibits the gain-of-function of the molecule- and genome-editing technology. Research on IEI will surely lead to a better understanding of other immune-related disorders including rheumatic diseases and atopic disorders.

原发性免疫缺陷(PID)是一种遗传性疾病与缺陷的一个重要组成部分的免疫系统。经典PID被认为是一种免疫系统功能丧失的疾病。最近的研究揭示了免疫功能障碍与自身免疫、自身炎症、过敏或恶性肿瘤易感性。其中一些是由免疫功能增强或免疫调节缺陷引起的。在此背景下,在国际免疫学会联合会(IUIS)的分类中,先天性免疫错误(IEI)一词现在被用来指代PID。到目前为止,已经在IEI患者中发现了400多个相关基因,重要的是,最近发现的许多基因是由异源突变引起的。此外,发病不一定是在儿童时期,我们开始看到越来越多的IEI患者在成年后被诊断出来。遗传分析的最新进展,包括全外显子组分析、全基因组分析和RNA-seq,有助于识别致病基因突变。我们也开始发现,即使在同一家族中具有相同突变的患者中,表型也存在异质性,这使我们怀疑修饰基因或表观遗传修饰是否参与了发病机制。相反,我们积累了许多病例,表明遗传异质性与表型同质性有关。因此,仅从某种类型的IEI的表型推断出负责任的基因变得困难。目前治疗IEI的方法包括造血细胞移植和基因治疗。其他治疗方式已经等待了很长时间,并将在未来引入。其中包括一种抑制分子和基因组编辑技术功能获得的小分子。对IEI的研究肯定会导致更好地理解其他免疫相关疾病,包括风湿病和特应性疾病。
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引用次数: 13
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