Long-term safety of subcutaneous immunotherapy with TO-204 in Japanese patients with house dust mite-induced allergic rhinitis and allergic bronchial asthma: Multicenter,open label clinical trial

Background

To evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial.

Guidelines for the use of human immunoglobulin therapy in patients with primary immunodeficiencies in Latin America

Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects.     

Suppression of immunoglobulin production in human peripheral blood mononuclear cells by monocytes via secretion of heavy-chain ferritin

In vitro antigen stimulation of peripheral blood mononuclear cells (PBMCs) does not induce immunoglobulin (Ig) production. However, pretreatment of PBMCs with l-leucyl-l-leucine methyl ester (LLME) prior to in vitro stimulation removes the suppression of Ig production. In the present study, we attempted to identify the target cells of LLME and determine the mechanisms by which Ig production in PBMCs is suppressed. We found that CD14⁺ monocytes are involved in the suppression of Ig production in PBMCs. Furthermore, we confirmed that heavy-chain ferritin derived from CD14⁺ monocytes suppresses Ig production in PBMCs, possibly through iron sequestration.     

IgH和IgL引物联合检测对提高石蜡组织淋巴瘤基因重排检出率的价值

背景与目的：通过聚合酶链反应（polymerase chain reaction,PCR）扩增免疫球蛋白重链（immunoglobulin heavy chain,IgH）基因对其克隆性的检测,可以辅助诊断淋巴瘤。缺点是假阴性率较高,在石蜡包埋组织中尤为明显。本研究拟采用手工显微切割、免疫球蛋白重链和轻链（immunoglohulin light chain,IgL）联合测定等方式,探讨该方法在石蜡包埋组织中非霍奇金淋巴瘤（non-Hodgkin’s lymphoma,NHL）诊断中的价值。方法：选用1对IgH引物、1对T细胞受体γ（Tcell receptor γ,TCRγ）、TCRγ引物、2对新设计的轻链引物,通过PCR、琼脂糖和聚丙烯酰胺凝胶电泳（PAGE）及银染技术,检测经形态学及免疫组织化学确诊的58例石蜡包埋组织标本,包括39例B细胞淋巴瘤、16例T细胞淋巴瘤和3例淋巴结反应性增生组织。以DG75和Jurkat淋巴瘤细胞系DNA作为对照。结果：IgH引物P1在39例B细胞淋巴瘤检出阳性率79．5％（31／39）。假阳性率6．25％（1／16）,IgL引物在B细胞淋巴瘤检出阳性率71．8％（28／39）。假阳性率12．5％（2／16）,经统计学分析二者检出率无显著性差异（P〉0．05）。二者联合检测,B细胞淋巴瘤阳性检出率可以达到92．3％,假阳性率并无明显提高（12．5％）。以上重排引物在反应性增生淋巴结组织中均未检出。结论：IgH与IgL引物联合检测可明显提高石蜡包埋组织中B细胞淋巴瘤的检出率,并为B-NHL的诊断及鉴别诊断提供了有效的辅助手段。     

IgG4相关性脑膜病变

目的探讨Ig G4相关性脑膜病变的临床病理学特征以及诊断与鉴别诊断要点。方法与结果男性患者,49岁,临床表现为头痛近2年并进行性加重1月余,头部MRI显示左侧顶叶占位性病变,增强扫描可见"脑膜尾征",手术完整切除病灶。组织学形态,左侧顶叶硬脑膜和脑实质大量胶原纤维增生,其间散在灶状细胞浸润,多为较成熟的浆细胞,部分浆细胞内可见匀质红染的Russell小体,其间散在淋巴细胞和少量嗜酸性粒细胞,局部可见小灶状坏死,间质纤维母细胞和小血管增生,未见包膜,病变累及周围脑组织。免疫组织化学染色,浆细胞胞质弥漫性表达Ig G和Ig G4(60%)、胞膜表达CD38和CD138,淋巴细胞胞膜表达CD3、CD4或CD20。血清Ig G4为1.05 g/L。最终病理诊断为(左侧顶叶)Ig G4相关性脑膜病变可能性大。术后予抗感染、抗癫、营养支持治疗,症状明显好转,出院后未按医嘱定期随访。结论 Ig G4相关性脑膜病变临床少见,且缺乏典型临床表现和特征性影像学改变,术前诊断与鉴别诊断困难,血清Ig G4水平升高是其诊断的重要线索,明确诊断仍需依靠特征性的组织学形态和免疫组织化学表型。     

Immunoglobulin variable gene analysis of human autoantibodies reveals antigen-driven immune response to glutamate decarboxylase in type 1 diabetes mellitus

Insulin-dependent (type 1) diabetes mellitus is an organ-specific autoimmune disease frequently associated with an islet-specific humoral autoimmune response. The role of islet cell autoantibodies in the disease process is unclear; in particular, it is not known whether they are a non-specific side effect of islet cell destruction or play a role in the autoimmune network leading to type 1 diabetes. Here we report the immunoglobulin gene usage and somatic mutation rates of a panel of seven human monoclonal islet cell autoantibodies (MICA 1–7) directed towards the major islet cell autoantigen glutamate decarboxylase (GAD). These autoantibodies were produced from cells from two patients with newly diagnosed type 1 diabetes. VH1, VH4 and Vλ2 gene segments were frequently used in the MICA, but no correlation between V gene usage and epitope recognition was found. The nonrandom ratio of replacement versus silent mutations in the variable gene region, an accumulation of replacement mutations in the complementarity determining regions, which confer antigen binding, and the high relative avidity for GAD observed for MICA 1, 3, 4, and 6, suggested that the immune response to GAD is driven by the antigen. In contrast, MICA 2, 5, and 7, revealing a lower affinity for antigen, have accumulated a large number of silent mutations. These latter antibodies may, therefore, be characteristic for later stages of the chronic autoimmune disease. Our results argue in favor of an antigen-driven autoantibody response to islets in human type 1 diabetes. They suggest that GAD is an important target of autoimmunity associated with type 1 diabetes.     

化学法交联人-人抗体用于抗甲型肝炎病毒IgM抗体检测质控品的研究

生部临床检验中心发放的抗-HAV IgM质控品相当,S/CO值分别为2.96、3.12,能够作为抗-HAV IgM检测的阳性质控.该嵌合抗体在4℃及-20℃条件下均能稳定保存至少6周.IgG、IgM及交联剂不影响嵌合抗体的阳性检测结果,且该嵌合抗体与抗-HBc IgM、抗-HEV IgM检测不存在交叉反应.使用临床上常见的检测试剂盒检测结果均为阴性.结论 通过化学交联的方法成功构建了人-人嵌合抗体,可用作为抗-HAV IgM检测质控物.