HIF-1 相关信号通路及其在自身免疫性疾病中作用

自身免疫性疾病(AID)是一类由自身抗原引起自身组织损伤的疾病。目前治疗AID仍以对症治疗和控制病情进展的药物为主,缺乏有效治疗措施,从而造成其致死率较高、治愈率较低的现状。因此对AID发病机制的详细阐明,在AID患者的临床及预后中都至关重要。许多研究表明缺氧诱导因子-1(HIF-1)参与AID的发病过程,本文将近年来关于HIF-1相关的信号通路及其在AID中作用的研究进展作一综述,以期为AID的临床治疗提供依据。     

HLA-Ⅱ类基因与人类疾病相关性研究进展

通过DNA分型技术 ,已经明确了多种疾病的发生和发展与HLA Ⅱ类基因相关联。可通过计算相对危险因子 (RR)来判断HLA等位基因的频率。HLA Ⅱ类基因多态性可以改变HLA分子、抗原、T细胞之间相互作用的特性 ,并因此控制对外来抗原 (有时自身抗原 )的免疫应答。HLA Ⅱ类基因的编码的某一氨基酸序列控制着对疾病的易感性和临床性状。构成HLA基因群的各个基因是高度连锁的 ,因而与某一特定疾病关联的易感基因有可能不是单一的 ,而是一些连锁基因的组合。     

DNA疫苗在自身免疫性疾病中的研究进展

自身免疫性疾病(autoimmune disease,AID)是一类因机体免疫耐受功能受损而致免疫细胞及其成分对自身组织结构和功能破坏,并出现一定临床表现的疾病。AID发病机制复杂,尚缺乏有效的治疗手段,因而严重影响患者的生活质量。基因疫苗又称DNA疫苗,从wolff等人首次提出至今,已在预防感染、AID及肿瘤等相关领域的研究中取得显著成效。本文就DNA疫苗在AID治疗中的应用及研究进展做一综述,以期为AID的临床治疗提供理论依据。     

沈阳地区汉族人群HLA-DRB1的PCR-SBT分型研究

HLA(humanleukocyteantigen ,HLA)位于人类第 6号染色体短臂 6p2 1.3区域 ,具有高度的遗传多态性 ,作为个体组织细胞的遗传标志物 ,在抗原识别、递呈、免疫应答与调控等方面起着非常重要的作用。其中HLA DR抗原是异基因移植免疫反应中最重要的抗原之一 ,决定其特异性的主要编码基因DRB1座位具有高度多态性 ,DRB1基因分型对器官移植的供体选择、法医学个体认定、HLA与疾病相关性及人类学等研究均具有重要意义。我们用聚合酶链反应 直接测序方法 (PCR SBT)对沈阳地区汉族健康个体进行了DRB1高分辨率的等位基因分析。沈阳地区汉族…     

活化诱导的胞嘧啶核苷脱氨酶与免疫球蛋白基因多样性及免疫性疾病的关系

类别转换重组(CSR)和体细胞高频突变(SHM)是活化的B淋巴细胞在免疫球蛋白基因组中启动第2次多样化进程的2个重要过程,然而活化诱导的胞嘧啶核苷脱氨酶(AID)是CSR和SHM过程中必需的酶.研究发现,AID在免疫球蛋白基因多样性中发挥重要作用,并且与免疫性疾病有关.现就AID与免疫球蛋白基因多样性及免疫性疾病之间的关系进行综述.     

091 HLA—Ⅱ类基石民人类疾病相关性研究进展

通过ＤＮＡ分型技术，已经明确了多疾病的发生和发展与ＨＬＡ－Ⅱ类基因相关联。可通过计算相对危险因子（ＲＲ）来判断ＨＬＡ等基因的频率。ＨＬＡ－Ⅱ类基因多态性可以改变ＨＬＡ分子、抗原、Ｔ细胞之间相互作用的特性，并因此控制对外来抗原（有时自身抗原（）的免疫应答。ＨＬＡ－Ⅱ类基因的编码的某一氨基酸序列控制着对疾 易感性和临床性状。构成ＨＬＡ基因群的各个基因是高度连锁的，因而与某一特定疾病关联的易感基因有可     

中国广州人群中HBV感染与HLA-DRB1基因的相关性研究

ＨＬＡ系统在机体的免疫应答和免疫调节中发挥着重要的作用 ,Ⅱ类抗原递呈外源性抗原肽给ＣＤ4+ 辅助性Ｔ细胞 ,其多态性影响着个体的免疫应答和抗原多肽的递呈 ,与自身免疫性疾病和许多感染性疾病的易感性密切相关 ,是研究疾病易感性中不可忽视的遗传因素。本文采用经我们改进的套式ＰＣＲ ＳＳＰ方法对广州地区的 88名无血缘关系的乙肝患者 (ＨＢｓＡｇ、ＨＢｅＡｇ、ＨＢｃＡｂ检测阳性 )和 83名无血缘关系健康个体样品进行了ＨＬＡ ＤＲＢ1基因分型 ,寻找与ＨＢＶ感染的相关性。外引物位于内含子内 ,5′引物 :5′ ＡＧＣＧＧＡＧＴＧＧ…     

MDR1基因多态性对肝移植受体普乐可复治疗的影响

目的探讨普乐可复（Tacrolimus，FK506）服用剂量和血药浓度的个体差异与供受体多药耐药基因1（multidrug resistance gene 1，MDR1）多态性的关系。方法监测50例口服普乐可复的肝移植受体体重、服药剂量、全血谷浓度，用PCR-限制性片段长度多态性分析的方法检测供受体MDR1第3435位C／T基因型，计算每日每公斤体重的FK506用量和血药浓度与每日每公斤体重的FX505用量的比值，并分析与供受体MDR1基因型的关系。结果在各50例供受体研究中，23％为MDR1 CC基因型，54％为CT基因型，13％为TT基因型。MDR1 CC基因型受体的每日每公斤体重的FK506用量明显高于CT和TT基因型受体，前者血药浓度与每日每公斤体重的FK506用量的比值显著低于后两者，供体MDR1基因型对此无明显影响。结论普乐可复服用剂量和血药浓度与受体的MDR1第3435位点基因多态性相关。MDRI多态性分析可指导肝移植受体普乐可复临床用药的个体化。     

自身抗体谱数据挖掘及SLE预测模型的建立

目的 探讨自身抗体在系统性红斑狼疮(systemic lupus erythematosus,SLE)及其他自身免疫性疾病(autoimmune diseases,AID)中的阳性分布趋势和诊断价值.方法 回顾分析2015年1月至2016年9月绵阳市中心医院自身抗体谱(autoantibodies,AAB)检测病例10684例,其中SLE 801例,其他AID1564例,非AID8319例,观察16种自身抗体在不同性别、年龄和疾病中的阳性分布差异,分析自身抗体个案聚类结果与临床诊断的相关性及其对SLE的预测价值.结果 16种自身抗体在女性中的阳性率,除外Jo-1、Scl-70、PM-Scl和PCNA,均高于男性,差异有统计学意义(P<0.001);在≤20岁、21~49岁和≥50岁三个年龄组的阳性率,除外Jo-1、PM-Scl、PCNA和AMA-M2,差异均有统计学意义(P<0.001);在SLE的阳性率,除外Jo-1、CENP B、Scl-70和AMA-M2,均高于其他AID和非AID两个疾病对照组,差异有统计学意义(P<0.001).自身抗体个案聚类与临床诊断相关(r=0.603,Kappa=0.476).ANA(OR=2.96)和ds-DNA(OR=2.31)对SLE预测价值排前2位.Logistic模型预测SLE的Se 81.2%,Sp97.6%,LP73.5%,LN98.4%,Ac 96.4%.结论 自身抗体在不同性别、年龄和疾病中的分布存在差异,自身抗体谱表达模式具有聚类特征,多种自身抗体联合性别、年龄因素建立Logistic预测模型有助于SLE诊断.     

白细胞介素-6基因多态性与疾病的易感性

白细胞介素-6(interleukin-6,IL-6)作为一种多功能的炎症细胞因子,具有调节免疫应答、参与炎症反应、影响神经内分泌系统功能、活化破骨细胞等多种功能,参与了多种疾病的发生、发展。IL-6基因存在基因变异及基因多态性,这些基因多态性影响IL-6的转录和表达,造成个体间差异。IL-6基因还是多种临床疾病的相关基因,其基因多态性亦与这些临床疾病的易感性及发病机制相关。本文对IL-6的基因多态性与相关疾病的研究进展做一综述。     

AID Biology: A pathological and clinical perspective

Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs). The beneficial physiological role of AID in antibody diversification is outweighed by its detrimental role in the genesis of several chronic immune diseases, under non-physiological conditions. This review offers a comprehensive and better understanding of AID biology and its pathological aspects, as well as addresses the challenges involved in AID-related cancer therapeutics, based on various recent advances and evidence available in the literature till date. In this article, we discuss ways through which our interpretation of AID biology may reflect upon novel clinical insights, which could be successfully translated into designing clinical trials and improving patient prognosis and disease management.     

Seronegative autoimmune diseases: A challenging diagnosis

Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren’s syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.     

Autopolyreactivity Confers a Holistic Role in the Immune System

In this review, we summarize and discuss some key findings from the study of naturally occurring autoantibodies. The B‐cell compartment of the immune system appears to recognize almost all endogenous and environmental antigens. This ability is accomplished principally through autopolyreactive humoral and cellular immune receptors. This extended autopolyreactivity (1) along immunoglobulin gene recombination contributes to the immune system's ability to recognize a very large number of self and non‐self constituents; and (2) generates a vast immune network that creates communication channels between the organism's interior and exterior. Thus, the immune system continuously evolves depending on the internal and external stimuli it encounters. Furthermore, this far‐reaching network's existence implies activities resembling those of classical biological factors or activities that modulate the function of other classical biological factors. A few such antibodies have already been found. Another important concept is that natural autoantibodies are highly dependent on the presence or absence of commensal microbes in the organism. These results are in line with past and recent findings showing the fundamental influence of the microbiota on proper immune system development, and necessitate the existence of a host – microbe homeostasis. This homeostasis requires that the participating humoral and cellular receptors are able to recognize self‐antigens and commensal microbes without damaging them. Autopolyreactive immune receptors expressing low affinity for both types of antigens fulfil this role. The immune system appears to play a holistic role similar to that of the nervous system.     

Presence of C1q-reactive immune complexes in patients with leprosy

Presence of soluble immune complexes was investigated in sera from persons with a well documented clinical diagnosis of leprosy. The complexes were detected by their reactivity with the C1q component of complement.

More than 70% of the studied patients with lepromatous-leprosy had immune complexes demonstrable by this method (39/51), while only a small proportion of the healthy control group (1/35 or about 3%) had precipitable complexes. Two out of nine sera from patients with tuberculoid leprosy reacted when tested with C1q component. The presence of free-antibody to mycobacterial antigens was determined as well. The possible relationship between the presence of such immune complexes and the pathology of some reactional states of the disease is discussed.

     

间充质干细胞在自身免疫性疾病中的应用研究进展

自身免疫性疾病（AID）的发病机制主要在于机体自身耐受的破坏,机体产生自身抗体和（或）自身反应性淋巴细胞,导致疾病的发生。目前临床上对AID的治疗主要是采取非特异性免疫抑制。虽然一定程度上可减轻症状,但不能根治疾病,而重症AID缺乏理想的治疗方法,预后差。因此,寻找有效的治疗方法仍然是目前临床亟待解决的问题。间充质干细胞（MSC）是一种非造血多能成体干细胞,具有多向分化以及促进组织修复等潜能,其免疫调控作用的发现是近年来干细胞研究领域的一项重要突破。最近,MSC移植治疗自身免疫性疾病的应用研究不断涌现,显示了MSC的免疫调节特性及其治疗AID的潜在能力,为进一步研究奠定了基础。     

The role of the innate immune response in autoimmune disease

Autoimmune diseases are the clinical correlate of a dysregulation of the immune system, involving multiple steps and multiple components of both the innate and the adaptive immune system. Innate immune cells are sensitive to a very limited repertoire of foreign "patterns" that bind to selective "pattern recognition receptors". In contrast, adaptive auto-reactive T or B cells bear receptors specific for antigens including "self" antigens and are rendered non-reactive by several "quality control" mechanisms. Under special conditions, activation of cells of the innate immune system can break the state of inactivity of auto-reactive cells of the adaptive immune system, thereby provoking autoimmune disease. Here we review examples to illustrate how innate immune activation influences autoimmune disease and point to the implications for the treatment of human autoimmune disease.