• 【IgA天疱疮的vegetans变体,IgA天疱疮和其他自身免疫性水疱性疾病的变体。】 复制标题 收藏 收藏
    DOI:10.1097/DAD.0b013e318278d419 复制DOI
    作者列表:Wolz MM,Camilleri MJ,McEvoy MT,Bruce AJ
    BACKGROUND & AIMS: :Pyodermatitis-pyostomatitis vegetans (PPV) constitutes an inflammatory mucocutaneous dermatosis that is associated with inflammatory bowel disease. Clinically, PPV appears as pustules on mucosal surfaces and as vegetating exudative plaques on intertriginous surfaces. It is typically a clinical diagnosis supported by histological findings. Microscopic findings include epidermal hyperplasia, focal acantholysis, and a dense mixed inflammatory infiltrate with intraepithelial and subepithelial eosinophilic microabscesses. In the recent literature, immunofluorescence has been thought to be negative in PPV or, if positive, an aberrant finding. Herein, we report 2 cases of PPV associated with inflammatory bowel disease, which display intercellular IgA deposits. Although these cases may represent isolated epiphenomena, it is possible that the paucity of PPV cases with immunofluorescent studies hitherto has led to an oversight of an interesting association between intercellular IgA and PPV.
    背景与目标: : 脓性皮炎-脓性口炎 (PPV) 构成炎症性粘膜皮肤皮肤病,与炎症性肠病有关。临床上,PPV表现为粘膜表面的脓疱和三叉间表面的植被渗出性斑块。通常是由组织学发现支持的临床诊断。显微镜检查结果包括表皮增生,局灶性棘层松解和上皮内和上皮下嗜酸性微脓肿的致密混合炎性浸润。在最近的文献中,免疫荧光被认为在PPV中是阴性的,或者如果是阳性的,则是异常的发现。在此,我们报告了2例与炎症性肠病相关的PPV病例,这些病例显示出细胞间IgA沉积。尽管这些病例可能代表孤立的现象,但迄今为止,通过免疫荧光研究的PPV病例很少,这可能导致对细胞间IgA和PPV之间有趣的关联的监督。
  • 【两种类风湿关节炎特异性自身抗原将微生物免疫与关节的自身免疫反应相关联。】 复制标题 收藏 收藏
    DOI:10.1172/JCI93450 复制DOI
    作者列表:Pianta A,Arvikar SL,Strle K,Drouin EE,Wang Q,Costello CE,Steere AC
    BACKGROUND & AIMS: :In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels. FLNA did not show the same results. The HLA-DR-presented GNS peptide has marked sequence homology with epitopes from sulfatase proteins of the Prevotella sp. and Parabacteroides sp., whereas the HLA-DR-presented FLNA peptide has homology with epitopes from proteins of the Prevotella sp. and Butyricimonas sp., another gut commensal. Patients with T cell reactivity with each self-peptide also had responses to the corresponding microbial peptides, and the levels were directly correlated. Furthermore, HLA-DR molecules encoded by shared-epitope (SE) alleles were predicted to bind these self- and microbial peptides strongly, and these responses were more common in RA patients with SE alleles. Thus, sequence homology between T cell epitopes of 2 self-proteins and a related order of gut microbes may provide a link between mucosal and joint immunity in patients with RA.
    背景与目标: : 在类风湿关节炎 (RA) 中,粘膜部位的免疫触发因素 (例如肠道菌群) 可能会促进自身免疫,从而影响关节。在这里,我们使用基于发现的蛋白质组学来检测滑膜或外周血单核细胞中hla-dr呈现的肽,并鉴定出2个自身抗原,N-acetylglucosamine-6-sulfatase (GNS) 和丝状蛋白A (FLNA),分别作为RA患者52% 和56% 中T细胞和b细胞反应的靶标。GNS和FLNA在滑膜中均高表达。GNS似乎是瓜氨酸,并且GNS抗体值与抗瓜氨酸蛋白抗体 (ACPA) 水平相关。FLNA没有显示相同的结果。Hla-dr表示的GNS肽与Prevotella sp。和Parabacteroides sp。的硫酸酯酶蛋白的表位具有明显的序列同源性,而hla-dr表示的FLNA肽与Prevotella sp的蛋白的表位具有同源性。和另一种肠道共生的Butyricimonas sp。与每个自身肽具有T细胞反应性的患者也对相应的微生物肽产生反应,并且水平直接相关。此外,由共享表位 (SE) 等位基因编码的hla-dr分子被预测会强烈结合这些自身肽和微生物肽,并且这些反应在具有SE等位基因的RA患者中更为常见。因此,2种自身蛋白的T细胞表位与肠道微生物的相关顺序之间的序列同源性可能在RA患者的粘膜和关节免疫之间提供联系。
  • 【使用脂质体传递代谢型谷氨酸受体的正变构调节剂来控制自身免疫性炎症。】 复制标题 收藏 收藏
    DOI:10.1002/jbm.a.36151 复制DOI
    作者列表:Gammon JM,Adapa AR,Jewell CM
    BACKGROUND & AIMS: :Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation. The therapeutic potential of PHCCC, however, is hindered by dose-limiting toxicity, poor solubility, and the need for frequent dosing. We hypothesized liposomal delivery of PHCCC might enable safe, effective delivery of this hydrophobic drug to exploit metabolism as a means of controlling inflammation in self-reactive immune cells. PHCCC was readily encapsulated in liposomes modified with polyethylene glycol. Under sink conditions, controlled release resulted in 58% of drug released into media over 18 hours. Culture of primary DCs with PHCCC liposomes reduced pro-inflammatory cytokine secretion while reducing toxicity four-fold compared with soluble PHCCC. During co-culture of DCs with myelin-reactive T cells from transgenic mice, PHCCC liposomes reduced T cell proliferation and interferon gamma secretion. These results support the potential of using liposomes to promote tolerance through biocompatible delivery of metabolic modulators. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2977-2985, 2017.
    背景与目标: 多发性硬化症 (MS) 是一种自身免疫性疾病,其中髓磷脂被错误地识别为外来物质并受到适应性免疫系统的攻击。树突状细胞 (dc) 通过向T细胞呈递抗原来指导适应性免疫,因此可作为自身免疫疗法的靶标。N-Phenyl-7-(羟基亚氨基) 环丙 [b]chromen-1a-carboxamide (PHCCC) 是代谢型谷氨酸受体4 (mGluR4) 的正变构调节剂,可以通过改变细胞因子分泌来促进调节性T细胞分化。然而,PHCCC的治疗潜力受到剂量限制毒性,溶解度差以及需要频繁给药的阻碍。我们假设PHCCC的脂质体递送可能使这种疏水药物的安全,有效的递送能够利用代谢作为控制自我反应免疫细胞中炎症的手段。PHCCC很容易封装在用聚乙二醇修饰的脂质体中。在下沉条件下,受控释放导致药物在18小时内释放到培养基中的58%。与可溶性PHCCC相比,用PHCCC脂质体培养原代dc可减少促炎性细胞因子的分泌,同时降低毒性的四倍。在dc与转基因小鼠的髓磷脂反应性T细胞共培养期间,PHCCC脂质体降低了T细胞的增殖和干扰素 γ 的分泌。这些结果支持了使用脂质体通过代谢调节剂的生物相容性递送来促进耐受性的潜力。©2017威利期刊公司J生物材料Res部分A: 105A: 2977-2985,2017。
  • 【在证明并非如此之前,一切都是自身免疫的。】 复制标题 收藏 收藏
    DOI:10.1007/s12016-013-8385-8 复制DOI
    作者列表:Shoenfeld Y
    BACKGROUND & AIMS: :It is astounding to consider that virtually, every textbook of physiology in every medical school in the world does not include a chapter on immunology. On the other hand, virtually, in every textbook in internal medicine, immunology and immune response overlaps with every tissue and every organ. Indeed, historically, the concept of the immune response was recognized primarily in the setting of allergy and/or anaphylaxis. Indeed, the very concepts of infection, microbiology and host protection are relatively new sciences. In fact, it was little more than 100 years ago when washing hands became what is now coined "standard of care." How different it is in 2013, where one finds Handi Wipes for shoppers to use at grocery stores to protect themselves from the flora on shopping cart handles. Autoimmunity is even a newer concept without going into the well-known history of Paul Ehrlich and hemolytic anemias, the LE cell, and the beginning field of serology (and rheumatoid factor discovery). It is apparent that our understanding of autoimmunity has become linked hand-in-glove with new tools and investigational probes into serology and, more recently, the cellular immune response. With such discoveries, a number of key observations stand out. Firstly, there are a great deal more autoantibodies than there are autoimmune diseases. Second, there are a great deal more of autoimmune diseases than was believed in 1963 on the occasion of the publication of the first textbook of autoimmune diseases. Third, autoimmune diseases are, for the most part, orphan diseases, with many entities afflicting too few patients to excite the financial limb of pharmaceutical companies. In this special issue, we have grouped a number of papers, many of which were presented at the recent Congress of Autoimmunity that focus on issues that are not commonly discussed in autoimmunity. It reminds us that due to the ubiquitous nature of the innate and adaptive response, that there are a large number of diseases that have either an inflammatory and/or specific autoimmune response, we have to keep an open eye because everything is potentially autoimmune until proven otherwise.
    背景与目标: : 令人震惊的是,实际上,世界上每所医学院的每本生理学教科书都没有包含有关免疫学的章节。另一方面,实际上,在内科的每一本教科书中,免疫学和免疫反应与每个组织和每个器官都重叠。事实上,从历史上看,免疫反应的概念主要在过敏和/或过敏反应的背景下被认可。实际上,感染,微生物学和宿主保护的概念是相对较新的科学。实际上,大约在100年前,洗手已成为现在创造的 “护理标准”。2013年有多不同,在那里人们可以找到Handi湿巾供购物者在杂货店使用,以保护自己免受购物车手柄上的植物的侵害。自身免疫甚至是一个较新的概念,而无需深入保罗·埃里希 (Paul Ehrlich) 和溶血性贫血,LE细胞以及血清学 (和类风湿因子发现) 的开始领域。很明显,我们对自身免疫的理解已与新工具和血清学研究以及最近的细胞免疫反应的研究联系在一起。有了这样的发现,许多关键观察结果脱颖而出。首先,自身抗体比自身免疫性疾病要多。其次,自身免疫性疾病的数量比第一本自身免疫性疾病教科书出版时所1963年的要多。第三,自身免疫性疾病在很大程度上是孤儿疾病,许多实体折磨的患者太少,无法激发制药公司的财务分支。在本期特刊中,我们对许多论文进行了分组,其中许多论文是在最近的自身免疫大会上发表的,这些论文的重点是在自身免疫中通常不讨论的问题。它提醒我们,由于先天反应和适应性反应的普遍存在,有大量的疾病具有炎症和/或特异性自身免疫反应,我们必须睁大眼睛,因为一切都是潜在的自身免疫,直到证明不是。
  • 【Β-拉帕酮改善实验性自身免疫性脑脊髓炎。】 复制标题 收藏 收藏
    DOI:10.1016/j.jneuroim.2012.09.004 复制DOI
    作者列表:Xu J,Wagoner G,Douglas JC,Drew PD
    BACKGROUND & AIMS: :β-Lapachone is a naturally occurring quinine, originally isolated from the bark of the lapacho tree (Tabebuia avellanedae) which is currently being evaluated in clinical trials for the treatment of cancer. In addition, recent investigations suggest its potential application for treatment of inflammatory diseases. Multiple sclerosis (MS) is an autoimmune disorder characterized by CNS inflammation and demyelination. Reactive T cells including IL-17 and IFN-γ-secreting T cells are believed to initiate MS and the associated animal model system experimental autoimmune encephalomyelitis (EAE). IL-12 family cytokines secreted by peripheral dendritic cells (DCs) and CNS microglia are capable of modulating T-cell phenotypes. The present studies demonstrated that β-lapachone selectively inhibited the expression of IL-12 family cytokines including IL-12 and IL-23 by DCs and microglia, and reduced IL-17 production by CD4(+) T-cells indirectly through suppressing IL-23 expression by microglia. Importantly, our studies also demonstrated that β-lapachone ameliorated the development on EAE. β-Lapachone suppression of EAE was associated with decreased expression of mRNAs encoding IL-12 family cytokines, IL-23R and IL-17RA, and molecules important in Toll-like receptor signaling. Collectively, these studies suggest mechanisms by which β-lapachone suppresses EAE and suggest that β-lapachone may be effective in the treatment of inflammatory diseases such as MS.
    背景与目标: : β-Lapachone是一种天然存在的奎宁,最初是从lapacho树 (Tabebuia avellanedae) 的树皮中分离出来的,目前正在治疗癌症的临床试验中进行评估。此外,最近的研究表明其在治疗炎症性疾病中的潜在应用。多发性硬化症 (MS) 是一种以中枢神经系统炎症和脱髓鞘为特征的自身免疫性疾病。包括IL-17和IFN-γ 分泌T细胞的反应性T细胞被认为会引发MS和相关的动物模型系统实验性自身免疫性脑脊髓炎 (EAE)。外周树突状细胞 (dc) 和CNS小胶质细胞分泌的IL-12家族细胞因子能够调节T细胞表型。本研究表明,β-lapachone选择性地抑制dc和小胶质细胞IL-12和IL-23等IL-12家族细胞因子的表达,并通过抑制小胶质细胞的IL-23表达间接降低CD4 () T细胞的IL-17产生。重要的是,我们的研究还表明 β-lapachone改善了EAE的发育。EAE的 β-Lapachone抑制与编码IL-12家族细胞因子,IL-23R和IL-17RA以及Toll样受体信号重要分子的mrna表达降低有关。总的来说,这些研究表明 β-拉帕酮抑制EAE的机制,并表明 β-拉帕酮可能有效治疗MS等炎症性疾病。
  • 【Anti-CD2单克隆抗体可预防实验性自身免疫性心肌炎的诱导。】 复制标题 收藏 收藏
    DOI:10.1536/jhj.41.507 复制DOI
    作者列表:Inomata T,Watanabe T,Haga M,Hirahara H,Abo T,Okura Y,Hanawa H,Kodama M,Izumi T
    BACKGROUND & AIMS: :We investigated the effect of a monoclonal antibody against CD2 molecules (OX34) in preventing the induction of experimental autoimmune myocarditis (EAM) induced by immunizing Lewis rats with cardiac myosin. Administration of OX34 before immunization, on Days -6, -4, -2 and 0, completely prevented EAM. On the other hand, treatment with OX34 just before the appearance of myocardial lesions, on Days 9, 11, 13 and 15, had only a partial effect in preventing the disease. Flow cytometric analysis of lymph node cells showed that CD3+ T cells were immediately depleted with the administration of OX34 but had largely recovered on Day 21. Lymph node cells in OX34-treated rats had no proliferative responses to cardiac myosin-rod, but the proliferation was restored when recombinant IL-2 was added. Ultimate production of the anti-myosin antibody was not inhibited by the treatment with OX34. These results suggest that the prevention of EAM by administering the anti-CD2 monoclonal antibody OX34 resulted from T cell depletion during the induction phase, and might in addition result from T cell anergy of Th1, but not Th2 cells.
    背景与目标: : 我们研究了针对CD2分子 (OX34) 的单克隆抗体在预防通过用心脏肌球蛋白免疫Lewis大鼠诱导的实验性自身免疫性心肌炎 (EAM) 中的作用。预防接种,在-6、-4、-2和0天给予OX34,完全预防了EAM。另一方面,在心肌病变出现之前,在第9、11、13和15天,用OX34治疗仅对预防该疾病有部分作用。淋巴结细胞的流式细胞术分析表明,CD3 T细胞在OX34的给药后立即耗尽,但在第21天已基本恢复。OX34-treated大鼠的淋巴结细胞对心肌肌球蛋白棒没有增殖反应,但添加重组IL-2后增殖得以恢复。用ox34处理不会抑制抗肌球蛋白抗体的最终产生。这些结果表明,通过施用anti-CD2单克隆抗体OX34来预防EAM是由于诱导期T细胞耗竭引起的,并且可能另外是由于Th1的T细胞无反应性,而不是Th2细胞。
  • 【耐受性构象在实验性自身免疫性重症肌无力中诱导口服耐受性的作用。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.165.7.3599 复制DOI
    作者列表:Im SH,Barchan D,Souroujon MC,Fuchs S
    BACKGROUND & AIMS: :We recently demonstrated that oral or nasal administration of recombinant fragments of the acetylcholine receptor (AChR) prevents the induction of experimental autoimmune myasthenia gravis (EAMG) and suppresses ongoing EAMG in rats. We have now studied the role of spatial conformation of these recombinant fragments in determining their tolerogenicity. Two fragments corresponding to the extracellular domain of the human AChR alpha-subunit and differing in conformation were tested: Halpha1-205 expressed with no fusion partner and Halpha1-210 fused to thioredoxin (Trx), and designated Trx-Halpha1-210. The conformational similarity of the fragments to intact AChR was assessed by their reactivity with alpha-bungarotoxin and with anti-AChR mAbs, specific for conformation-dependent epitopes. Oral administration of the more native fragment, Trx-Halpha1-210, at the acute phase of disease led to exacerbation of EAMG, accompanied by an elevation of AChR-specific humoral and cellular reactivity, increased levels of Th1-type cytokines (IL-2, IL-12), decreased levels of Th2 (IL-10)- or Th3 (TGF-beta)-type cytokines, and higher expression of costimulatory factors (CD28, CTLA4, B7-1, B7-2, CD40L, and CD40). On the other hand, oral administration of the less native fragments Halpha1-205 or denatured Trx-Halpha1-210 suppressed ongoing EAMG and led to opposite changes in the immunological parameters. It thus seems that native conformation of AChR-derived fragments renders them immunogenic and immunopathogenic and therefore not suitable for treatment of myasthenia gravis. Conformation of tolerogens should therefore be given careful attention when considering oral tolerance for treatment of autoimmune diseases.
    背景与目标: : 我们最近证明,口服或鼻腔给予乙酰胆碱受体 (AChR) 的重组片段可防止实验性自身免疫性重症肌无力 (EAMG) 的诱导,并抑制大鼠正在进行的EAMG。我们现在已经研究了这些重组片段的空间构象在确定其耐受性中的作用。测试了与人achrα 亚基的胞外域相对应且构象不同的两个片段: Halpha1-205在没有融合伴侣的情况下表达,Halpha1-210与硫氧还蛋白 (Trx) 融合,并指定为Trx-Halpha1-210。片段与完整AChR的构象相似性通过其与 α-bungarotoxin和抗AChR mab的反应性来评估,这些抗体对构象依赖性表位具有特异性。Trx-Halpha1-210,在疾病的急性期口服更天然的片段导致EAMG恶化,伴随着AChR特异性体液和细胞反应性的升高,Th1-type细胞因子 (IL-2,IL-12) 的水平升高,th2 (IL-10) 或Th3 (TGF-β) 型细胞因子水平降低,共刺激因子 (CD28,CTLA4,B7-1,B7-2,CD40L和CD40) 表达升高。另一方面,Halpha1-205或变性Trx-Halpha1-210的较低天然片段的口服给药抑制了正在进行的EAMG,并导致免疫学参数的相反变化。因此,似乎AChR衍生片段的天然构象使它们具有免疫原性和免疫致病性,因此不适合治疗重症肌无力。因此,在考虑口服耐受性治疗自身免疫性疾病时,应特别注意耐受性的构象。
  • 【阿仑单抗治疗多发性硬化后获得性血友病A和其他自身免疫性疾病: 两例报告。】 复制标题 收藏 收藏
    DOI:10.1016/j.msard.2020.102181 复制DOI
    作者列表:Comini-Frota ER,Campos APF,Neto APG,Christo PP
    BACKGROUND & AIMS: :Alemtuzumab (ALZ) is an anti-CD52 monoclonal antibody used to treat recurrent remittent multiple sclerosis (RRMS). After ALZ infusion, there is a depletion of T and B cells expressing CD52, while the stem cells and innate immune cells are spared. Longitudinal studies with long periods of follow-ups have reported ALZ-associated autoimmune diseases, such as thrombocytopenic purpura and thyroiditis. We report two patients who developed autoimmune hemophilia A or acquired hemophilia (AHA) after ALZ infusion, one of whom developed severe vitiligo. To the best of our knowledge, these two cases of ALZ-associated AHA are the first two cases to be reported in Brazil, and the fourth and fifth AHA cases to be reported worldwide. AHA is a potential life-threatening disease if not diagnosed and treated in a timely manner. The development of AHA should be cited as a possible adverse event, and specific coagulation tests must be part of the official recommendations for patient follow-ups.
    背景与目标: : Alemtuzumab (ALZ) 是一种anti-CD52单克隆抗体,用于治疗复发性缓解多发性硬化症 (RRMS)。ALZ输注后,表达CD52的T和b细胞耗竭,而干细胞和先天免疫细胞则得以幸免。长期随访的纵向研究报告了与ALZ相关的自身免疫性疾病,例如血小板减少性紫癜和甲状腺炎。我们报告了两名在输注ALZ后发展为自身免疫性血友病A或获得性血友病 (AHA) 的患者,其中一名患者发展为严重白癜风。据我们所知,这两个与ALZ相关的AHA病例是巴西报告的前两个病例,也是全球报告的第四和第五个AHA病例。如果不及时诊断和治疗,AHA是一种潜在的威胁生命的疾病。AHA的发展应被认为是可能的不良事件,并且特定的凝血测试必须是患者随访的官方建议的一部分。
  • 【诊断为自身免疫和相关疾病的患者的亲属和配偶患多发性硬化症的风险。】 复制标题 收藏 收藏
    DOI:10.1007/s10048-008-0156-y 复制DOI
    作者列表:Hemminki K,Li X,Sundquist J,Hillert J,Sundquist K
    BACKGROUND & AIMS: :In the era of complex disease genetics, the consideration of familial risks is important in the assessment of the likely success of these studies. In the present article, we study familial risks for multiple sclerosis (MS) among parents and offspring, singleton siblings, twins, and spouses when a family member was diagnosed with MS or any of 33 other autoimmune diseases. The availability of a Multigeneration Register in Sweden provides a reliable access to families throughout the last century. The diseases in individual family members were obtained through linkage to the Hospital Discharge Register. With a total patient population of 425,102 of whom 11,154 were diagnosed with MS, this is the largest population-based family study on these diseases to date. Standardized incidence ratio (SIR) was calculated for family member of MS patients compared to those lacking an affected family member. SIR for MS was 5.94 (6.12 when parents were aged <73 years) in offspring of affected parents, 6.25 in singleton siblings, 9.09 in twins, and 1.50 (nonsignificant) in spouses; the SIRs did not depend on the gender. The SIRs for MS were 1.84 when a parent was diagnosed with amyotrophic lateral sclerosis and 1.14 with parental asthma. The overall risk of MS was 1.21 when a parent was diagnosed with any autoimmune disease. The genes, so far associated with MS, explain little of the familial aggregation of MS, calling for further efforts in gene identification. The shared familial risks of MS with amyotrophic lateral sclerosis and asthma suggest shared genetic basis.
    背景与目标: : 在复杂疾病遗传学时代,对家族风险的考虑对于评估这些研究的可能成功至关重要。在本文中,我们研究了家庭成员被诊断出患有MS或33种其他自身免疫性疾病时,父母和后代,单身兄弟姐妹,双胞胎和配偶中多发性硬化症 (MS) 的家族风险。上个世纪,瑞典拥有多世代登记册,为家庭提供了可靠的访问途径。个别家庭成员的疾病是通过与医院出院登记册的联系获得的。共有425,102名患者,其中11,154名被诊断出患有MS,这是迄今为止针对这些疾病的最大的基于人群的家庭研究。与缺少受影响的家庭成员相比,计算了MS患者的家庭成员的标准化发病率 (SIR)。MS的SIR在受影响父母的后代中5.94 (6.12在父母年龄 <73岁时),在单身兄弟姐妹中6.25,在双胞胎中9.09,在配偶中1.50 (不显着); SIRs不取决于性别。当父母被诊断患有肌萎缩性侧索硬化症并1.14父母哮喘时,MS的SIRs被1.84。当父母被诊断患有任何自身免疫性疾病时,MS的总体风险1.21。到目前为止,与MS相关的基因几乎无法解释MS的家族聚集,因此需要进一步的基因鉴定努力。肌萎缩性侧索硬化症和哮喘的MS共同家族风险表明有共同的遗传基础。
  • 10 Autoimmune Polyglandular Syndrome type 2. 复制标题 收藏 收藏

    【自身免疫性多腺综合征2型。】 复制标题 收藏 收藏
    DOI:10.1590/1806-9282.65.12.1434 复制DOI
    作者列表:Martins SC,Venade G,Teixeira M,Olivério J,Machado J,Marques J,Matos LC
    BACKGROUND & AIMS: :Autoimmune polyglandular syndrome type 2 (APS 2) is defined by the presence of Addison's disease (AD) associated with autoimmune thyroid disease and/or Type 1 diabetes mellitus (T1DM). It is a rare disease, affecting about 1.4-2 cases/100,000 inhabitants. Its less frequent clinical presentation is the combination of AD, Graves' disease, and T1DM. We present the case of a 42-year-old woman with a history of total thyroidectomy due to Graves' disease, type 2 diabetes mellitus, and hypertension, who sought the ED due to asthenia, dizziness, nausea, and vomiting. She reported having stopped antihypertensive therapy due to hypotension and presented a glycemic record with frequent hypoglycemia. On physical examination, she had cutaneous hyperpigmentation. She had no leukocytosis, anemia, hypoglycemia, hyponatremia or hyperkalemia, and a negative PCR. Serum cortisol <0.5 ug/dl (4,3-22,4), urine free cortisol 9 ug/24h (28-214), ACTH 1384 pg/mL (4,7-48,8), aldosterone and renin in erect position of 0 pg/ml (41-323) and 430.7 uUI/ml (4.4-46.1) respectively. Quantiferon TB was negative; computerized axial tomography of the adrenals showed no infiltrations, hemorrhage, or masses. The 21-hydroxylase antibody assay was positive. B12 vitamin was normal, anti-GAD antibodies were positive, anti-insulin, anti-IA2, and anti-transglutaminase antibodies were all negative. The patient started insulin therapy and treatment for AD with prednisolone and fludrocortisone with good clinical response. This case aims to alert to the need for high clinical suspicion in the diagnosis of AD. Since this is a rare autoimmune disease, it is important to screen for other autoimmune diseases in order to exclude APS.
    背景与目标: : 自身免疫性多腺综合征2型 (APS 2) 的定义是与自身免疫性甲状腺疾病和/或1型糖尿病 (T1DM) 相关的Addison病 (AD) 的存在。这是一种罕见的疾病,影响约1.4-2例/100,000居民。其较不常见的临床表现是AD,graves病和T1DM的组合。我们介绍了一名42岁的女性,该女性因graves病,2型糖尿病和高血压而患有全甲状腺切除术,因虚弱,头晕,恶心和呕吐而寻求ED。她报告由于低血压而停止了抗高血压治疗,并出现了血糖记录,并伴有频繁的低血糖。体检时,她出现皮肤色素沉着。患者无白细胞增多,贫血,低血糖,低钠血症或高钾血症,PCR阴性。血清皮质醇 <0.5 ug/dl (4,3-22,4),尿游离皮质醇9 ug/24h (28-214),ACTH 1384 pg/mL (4,7-48,8),醛固酮和肾素的直立位置分别为0 pg/ml (41-323) 和430.7 uUI/ml (4.4-46.1)。Quantiferon TB阴性; 肾上腺的计算机轴向断层扫描显示没有浸润,出血或肿块。21-羟化酶抗体检测为阳性。维生素B12正常,抗GAD抗体阳性,抗胰岛素、anti-IA2、抗谷氨酰胺酶抗体均为阴性。患者开始胰岛素治疗,并使用泼尼松龙和氟氢可的松治疗AD,临床反应良好。该病例旨在提醒在诊断AD时需要高度临床怀疑。由于这是一种罕见的自身免疫性疾病,因此必须筛查其他自身免疫性疾病以排除APS。
  • 【出版商更正: Cxcl10 + 单核细胞定义了自身免疫性神经炎症期间中枢神经系统的致病亚群。】 复制标题 收藏 收藏
    DOI:10.1038/s41590-020-0742-1 复制DOI
    作者列表:Giladi A,Wagner LK,Li H,Dörr D,Medaglia C,Paul F,Shemer A,Jung S,Yona S,Mack M,Leutz A,Amit I,Mildner A
    BACKGROUND & AIMS: :An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    背景与目标: : 本文的修正案已经发表,可以通过本文顶部的链接进行访问。
  • 【住院患者的自身免疫性溶血性贫血: 450患者及其红细胞输血。】 复制标题 收藏 收藏
    DOI:10.1097/MD.0000000000018739 复制DOI
    作者列表:Chen C,Wang L,Han B,Qin L,Ying B
    BACKGROUND & AIMS: :Autoimmune hemolytic anemia (AIHA) is a rare disease in which autoantibodies target red blood cells (RBCs), leading to anemia that ranges from no symptoms to severe life-threatening hemolysis. Little is known about the severity of anemia, blood transfusion efficiency and risk of transfusion-related reactions among hospitalized AIHA patients, especially in those with incompatible RBC transfusions.A retrospective study was conducted among hospitalized AIHA patients from January 2009 to December 2015 in a large tertiary care medical center in southwest China.A total of 450 AIHA hospitalized patients were recruited, of whom 97.3% had warm AIHA, 30.3% had primary AIHA, and 90.7% were treated with corticosteroids. On admission, approximately 3% of patients had an hemoglobin (Hb) <30 g/L, 34% had an Hb between 30 and 59.9 g/L, and 46% had an Hb ranging from 60 to 89.9 g/L. A total of 2509.5 U RBCs were transfused to AIHA patients, and 14 transfusion-related adverse reactions were recorded, without any hemolytic transfusion reactions. With an average transfusion trigger of 52.0 ± 9.3 g/L, 59.7% of the patients received RBCs, and 55.8% of the transfusions were viewed as effective. Least incompatible RBCs were given in 39% of the transfusions, but the transfusion efficiency did not significantly decrease with these incompatible blood transfusions (P = .253). Primary AIHA patients with a nadir Hb of approximately 40 to 50 g/L during their hospital stay had the highest rate of remission and did not require a different total number of RBC transfusions (P = .068) or length of hospitalization (P = .194) compared to other groups with nadir Hb values <30 g/L, ≥30 and <40 g/L, ≥50 and <60 g/L, and ≥60 g/L.One-third of AIHA patients suffered from severe anemia during hospitalization, and transfusions, even with incompatible RBCs, were safe and efficient. However, transfusion triggers between 40 and 50 g/L seemed to benefit the most patients by alleviating the RBC destruction caused by autoantibodies, and a restrictive transfusion strategy was beneficial in AIHA patients.
    背景与目标: 自身免疫性溶血性贫血 (AIHA) 是一种罕见的疾病,其中自身抗体靶向红细胞 (rbc),导致贫血,从无症状到严重威胁生命的溶血。对住院AIHA患者贫血的严重程度,输血效率和输血相关反应的风险知之甚少,尤其是那些输注红细胞不相容的患者。一项回顾性研究是在中国西南一家大型三级医疗中心从2009年1月到2015年12月的住院AIHA患者中进行的。总共招募了450名AIHA住院患者,其中97.3% 名患有温热AIHA,30.3% 名患有原发性AIHA,90.7% 接受皮质类固醇治疗。入院时,约3% 的患者血红蛋白 (Hb) <30  g/L,34% 的Hb在30 ~ 59.9  g/L之间,46% 的Hb在60 ~ 89.9  g/L之间。共向AIHA患者输注2509.5例U红细胞,记录14例输血相关不良反应,无溶血性输血反应。平均输血触发52.0   ±   9.3  g/L,59.7% 的患者接受了红细胞,55.8% 的输血被认为是有效的。在39% 输血中给予最少不相容的红细胞,但这些不相容的输血并没有显著降低输血效率 (p   =  .253)。原发性AIHA患者在住院期间的最低Hb约为40至50  g/L,其缓解率最高,不需要不同的RBC输血总数 (p   =  .068) 或住院时间 (p   =  .194) 与其他具有最低Hb值的组相比 <30  g/L,≥ 30和 <40  g/L,≥ 50和 <60  g/L,≥ 60  g/L。三分之一的AIHA患者在住院期间出现严重贫血,输血,即使红细胞不相容,也是安全有效的。然而,40至50  g/L之间的输血触发似乎通过减轻自身抗体引起的RBC破坏而使大多数患者受益,并且限制性输血策略对AIHA患者有益。
  • 【自身免疫倾向MRL/MpJ-lpr小鼠血清中具有淀粉酶活性的抗体。】 复制标题 收藏 收藏
    DOI:10.1016/j.febslet.2006.08.036 复制DOI
    作者列表:Andryushkova AA,Kuznetsova IA,Orlovskaya IA,Buneva VN,Nevinsky GA
    BACKGROUND & AIMS: :Animals spontaneously developing lupus-like autoimmune pathology (SLE) are very promising models to study the mechanisms of natural abzymes (Abzs) generation and their role in etiology and pathogenesis of autoimmune diseases, but Abzs from the sera of animals remain virtually unstudied. In this work, electrophoretically homogeneous IgGs were isolated from the sera of MRL/MpJ-lpr mice. It was shown for the first time that amylase activity is an intrinsic property of antibodies (Abs) and their isolated heavy and light chains. Various markers of SLE pathology (proteinuria, enhanced concentration of anti-DNA Abs) increased with spontaneous development of SLE and especially after animal immunization, correlating with the increase in Abz relative amylase activity. The highest amylase activity was found in the sera Abs of healthy mice after delivery and at the beginning of lactation; this was not correlated with markers of mouse SLE but supports the idea that pregnancy could "activate" or "trigger" autoimmune-like manifestations and Abzs production in healthy mammals. The possible differences in mechanisms of Abzs production in lactating mice and animals developing SLE are discussed.
    背景与目标: : 自发发展为狼疮样自身免疫病理学 (SLE) 的动物是非常有前途的模型,用于研究自然酶 (Abzs) 产生的机制及其在自身免疫性疾病的病因和发病机理中的作用,但是来自动物血清的Abzs实际上仍未研究。在这项工作中,从MRL/MpJ-lpr小鼠的血清中分离出电泳均匀的igg。首次显示淀粉酶活性是抗体 (Abs) 及其分离的重链和轻链的固有特性。SLE病理的各种标志物 (蛋白尿,抗DNA Abs浓度增加) 随着SLE的自发发展而增加,尤其是在动物预防接种后,与Abz相对淀粉酶活性的增加有关。分娩后和哺乳期开始时,在健康小鼠的血清Abs中发现最高的淀粉酶活性; 这与小鼠SLE的标志物无关,但支持怀孕可以 “激活” 或 “触发” 健康哺乳动物的自身免疫样表现和abz产生的观点。讨论了哺乳期小鼠和发生SLE的动物中Abzs产生机制的可能差异。
  • 【将动物模型的数据转化为预防人类自身免疫性糖尿病的方法: 注意事项和初生非nocere。】 复制标题 收藏 收藏
    DOI:10.1006/clim.2001.5075 复制DOI
    作者列表:Greiner DL,Rossini AA,Mordes JP
    BACKGROUND & AIMS: :Type 1 diabetes in humans is a serious autoimmune disorder of children that is still poorly understood, unpreventable, and irreversible. Study of its animal models, notably the NOD mouse and BB rat, has generated a wealth of information concerning genetics and immunopathogenesis, but that information has still not altered the way in which we treat children with diabetes. In this review we attempt to identify the most promising avenues of continuing research in these models and the most important issues that must be faced by the designers of human therapies based on the animal dataset.
    背景与目标: : 人类的1型糖尿病是一种严重的儿童自身免疫性疾病,目前仍知之甚少,无法预防和不可逆转。对其动物模型 (尤其是NOD小鼠和BB大鼠) 的研究已经产生了有关遗传学和免疫病理的大量信息,但是这些信息仍然没有改变我们治疗糖尿病儿童的方式。在这篇综述中,我们试图确定在这些模型中继续研究的最有希望的途径,以及基于动物数据集的人类疗法设计者必须面对的最重要的问题。
  • 【原发性胆汁性肝硬化和自身免疫性肝炎的凋亡途径。】 复制标题 收藏 收藏
    DOI:10.1034/j.1600-0676.2001.021004272.x 复制DOI
    作者列表:Fox CK,Furtwaengler A,Nepomuceno RR,Martinez OM,Krams SM
    BACKGROUND & AIMS: BACKGROUND/AIMS:Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases with unknown etiologies that primarily target the liver. In both diseases, liver lesions are accompanied by large infiltrates of mononuclear cells. The purpose of this study was to determine if either the Fas-mediated or the granule-exocytosis pathways contribute to apoptosis in these diseases. METHODS:To determine the involvement of apoptosis in tissue injury we examined liver tissue for DNA fragmentation and morphological characteristics of apoptosis. The major cytotoxic pathways of activated lymphocytes were compared by quantitating the levels of transcripts for FasL and granzyme B, and expression was confirmed by immunoprecipitation of these molecules. RESULTS:In both diseases, apoptosis was observed. However, the main cell types undergoing apoptosis were hepatocytes in AIH, and biliary epithelial cells in PBC. In AIH the levels of FasL and granzyme B mRNA were increased over the levels detected in normal liver, while in PBC only the levels of granzyme B were elevated. Additionally, in AIH, the ratio of FasL transcripts to granzyme B transcripts was elevated, reflecting a possible increase in the relative contribution of FasL to the progression of the disease. Immunoprecipitation studies further support an increase in FasL protein expression in AIH. CONCLUSIONS:These data suggest that both FasL and granzyme B contribute to the apoptosis observed in AIH and PBC. However, FasL appears to play a more prominent role in the induction of hepatocyte apoptosis and tissue destruction in AIH.
    背景与目标:

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