• 【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。
  • 7 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:
  • 【携带脑源性肽的微粒可诱导T细胞耐受并改善实验性自身免疫性脑脊髓炎。】 复制标题 收藏 收藏
    DOI:10.1038/nbt.2434 复制DOI
    作者列表:Getts DR,Martin AJ,McCarthy DP,Terry RL,Hunter ZN,Yap WT,Getts MT,Pleiss M,Luo X,King NJ,Shea LD,Miller SD
    BACKGROUND & AIMS: :Aberrant T-cell activation underlies many autoimmune disorders, yet most attempts to induce T-cell tolerance have failed. Building on previous strategies for tolerance induction that exploited natural mechanisms for clearing apoptotic debris, we show that antigen-decorated microparticles (500-nm diameter) induce long-term T-cell tolerance in mice with relapsing experimental autoimmune encephalomyelitis. Specifically, intravenous infusion of either polystyrene or biodegradable poly(lactide-co-glycolide) microparticles bearing encephalitogenic peptides prevents the onset and modifies the course of the disease. These beneficial effects require microparticle uptake by marginal zone macrophages expressing the scavenger receptor MARCO and are mediated in part by the activity of regulatory T cells, abortive T-cell activation and T-cell anergy. Together these data highlight the potential for using microparticles to target natural apoptotic clearance pathways to inactivate pathogenic T cells and halt the disease process in autoimmunity.
    背景与目标: : 异常的T细胞活化是许多自身免疫性疾病的基础,但大多数诱导T细胞耐受的尝试都失败了。在先前利用天然机制清除凋亡碎片的耐受性诱导策略的基础上,我们发现抗原修饰的微粒 (直径500 nm) 在患有复发性实验性自身免疫性脑脊髓炎的小鼠中诱导长期T细胞耐受性。具体来说,静脉内输注聚苯乙烯或可生物降解的带有脑源性肽的聚 (丙交酯-共-乙交酯) 微粒可防止发作并改变疾病的进程。这些有益作用需要表达清道夫受体MARCO的边缘区巨噬细胞摄取微粒,并且部分由调节性T细胞的活性,流产性T细胞活化和T细胞无反应性介导。这些数据共同强调了使用微粒靶向自然凋亡清除途径以使致病性T细胞失活并阻止自身免疫中的疾病过程的潜力。
  • 【鉴定含有针对Barr体的抗体的自身免疫血清。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.151259598 复制DOI
    作者列表:Hong B,Reeves P,Panning B,Swanson MS,Yang TP
    BACKGROUND & AIMS: :Transcriptional inactivation of one X chromosome in mammalian female somatic cells leads to condensation of the inactive X chromosome into the heterochromatic sex chromatin, or Barr body. Little is known about the molecular composition and structure of the Barr body or the mechanisms leading to its formation in female nuclei. Because human sera from patients with autoimmune diseases often contain antibodies against a variety of cellular components, we reasoned that some autoimmune sera may contain antibodies against proteins associated with the Barr body. Therefore, we screened autoimmune sera by immunofluorescence of human fibroblasts and identified one serum that immunostained a distinct nuclear structure with a size and nuclear localization consistent with the Barr body. The number of these structures was consistent with the number of Barr bodies expected in diploid female fibroblasts containing two to five X chromosomes. Immunostaining with the serum followed by fluorescence in situ hybridization with a probe against XIST RNA demonstrated that the major fluorescent signal from the autoantibody colocalized with XIST RNA. Further analysis of the serum showed that it stains human metaphase chromosomes and a nuclear structure consistent with the inactive X in female mouse fibroblasts. However, it does not exhibit localization to a Barr body-like structure in female mouse embryonic stem cells or in cells from female mouse E7.5 embryos. The lack of staining of the inactive X in cells from female E7.5 embryos suggests the antigen(s) may be involved in X inactivation at a stage subsequent to initiation of X inactivation. This demonstration of an autoantibody recognizing an antigen(s) associated with the Barr body presents a strategy for identifying molecular components of the Barr body and examining the molecular basis of X inactivation.
    背景与目标: : 哺乳动物雌性体细胞中一个X染色体的转录失活导致无活性X染色体凝结成异色性染色质或Barr体。对于Barr体的分子组成和结构或导致其在雌性核中形成的机制知之甚少。由于自身免疫性疾病患者的人类血清通常包含针对多种细胞成分的抗体,因此我们认为某些自身免疫血清可能包含针对与Barr体相关的蛋白质的抗体。因此,我们通过人类成纤维细胞的免疫荧光筛选了自身免疫血清,并鉴定出一种对独特核结构进行免疫染色的血清,其大小和核定位与Barr体一致。这些结构的数量与包含2至5个X染色体的二倍体雌性成纤维细胞中预期的Barr体数量一致。用血清进行免疫染色,然后用针对XIST RNA的探针进行荧光原位杂交,表明来自自身抗体的主要荧光信号与XIST RNA共定位。对血清的进一步分析表明,它染色了人类中期染色体和与雌性小鼠成纤维细胞中无活性X一致的核结构。但是,它在雌性小鼠胚胎干细胞或雌性小鼠E7.5胚胎的细胞中没有显示出Barr体状结构的定位。雌性E7.5胚胎细胞中无活性X的染色不足,表明抗原可能在X失活开始后的某个阶段参与X失活。识别与Barr体相关的抗原的自身抗体的这种证明提出了一种识别Barr体分子成分并检查X失活的分子基础的策略。
  • 【儿童自身免疫性肝病的病理。】 复制标题 收藏 收藏
    DOI:10.1111/j.1872-034X.2007.00234.x 复制DOI
    作者列表:Kage M
    BACKGROUND & AIMS: :Liver disorders are more diverse in children than in adults, and autoimmune liver diseases also develop in childhood, although rarely. The autoimmune diseases in children comprise autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). The pathology of AIH and PSC is described. Although AIH in children is rare, it occurs in early childhood, and some elementary school students have been reported to develop cirrhosis. The histology of AIH in children is essentially the same as that in adults. We analyzed eight patients with childhood AIH. Four of these patients had a high AIH score, with typical histological features of AIH, that is, interface hepatitis with infiltration of lymphocytes and plasma cells, a severe necroinflammatory reaction and rosette formation of hepatocytes. Multinucleated hepatocytes were observed in three patients. This finding seems characteristic of childhood AIH, although rarely observed in adult AIH. Clinically, the distinction between AIH and PSC is often difficult in childhood, and the overlapping of both has also been reported. PSC-like histological features may be observed in some pediatric patients with AIH. In patients with acute onset of AIH, they show a pronounced necroinflammatory reaction in zone 3 (central area). Because an autoimmune phenomenon may occur in the early stage of childhood PSC, it is difficult to differentiate it from AIH in some patients. Some patients are diagnosed with AIH in the early stage, but with PSC during long-term follow up. The histopathological findings of childhood PSC are the same as those of adult PSC, and are characterized by biliary-type portal fibrosis and onion-like periductal fibrosis in medium-sized portal tracts.
    背景与目标: : 儿童的肝脏疾病比成人更加多样化,自身免疫性肝病也在儿童时期发展,尽管很少。儿童自身免疫性疾病包括自身免疫性肝炎 (AIH) 和原发性硬化性胆管炎 (PSC)。描述了AIH和PSC的病理。虽然儿童的AIH很少见,但它发生在儿童早期,据报道一些小学生会发展为肝硬化。儿童AIH的组织学与成人基本相同。我们分析了8例儿童AIH患者。这些患者中有4例具有较高的AIH评分,具有典型的AIH组织学特征,即界面肝炎伴淋巴细胞和浆细胞浸润,严重的坏死性炎症反应和肝细胞玫瑰花结形成。在三名患者中观察到多核肝细胞。这一发现似乎是儿童AIH的特征,尽管在成人AIH中很少观察到。临床上,AIH和PSC之间的区别在儿童时期通常很困难,并且也有报道称两者重叠。在某些小儿AIH患者中可能会观察到类似PSC的组织学特征。在AIH急性发作的患者中,他们在3区 (中央区域) 显示出明显的坏死性炎症反应。由于自身免疫现象可能发生在儿童PSC的早期,因此在某些患者中很难将其与AIH区分开。一些患者在早期被诊断为AIH,但在长期随访中被诊断为PSC。儿童PSC的组织病理学发现与成人PSC相同,其特征是胆道型门静脉纤维化和中型门静脉道的洋葱状导管周围纤维化。

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