Wu69-小鼠抗人白细胞介素2受体的单抗

本文报导应用杂交瘤技术制备的鼠抗人白细胞介素2受体(IL—2R)的单抗—Wu69.免疫沉淀表明它能识别分子量为56Kd的PHA活化的T细胞膜表面的蛋白分子。该抗体只对部分B细胞及非淋巴样生血细胞系呈阳性反应,而白血病T细胞系均为阴性,但对活化的T细胞及人T细胞克隆有高度的结合力。它可抑制T细胞的同种异体刺激所引起的增殖反应,并与IL—2有竞争作用。进一步应用FACS及顺序免疫沉淀试验证明它与抗Tac完全相同。 本文还对抗IL-2R的重要性及抗IL—2R作为免疫抑制剂的可喜前景进行了讨论。     

Efficacy and safety of anti-interleukin-5 therapy in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized,controlled trials

BackgroundAnti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear.MethodsA literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation.ResultsA total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n = 865; benralizumab, n = 1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86–0.97, I² = 0%). In addition, no significant differences in the changes in SGRQ scores and FEV₁ from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, ?0.86, 95% CI, ?1.92 – 0.19, I² = 0%; FEV₁, mean difference, 0.01, 95% CI, ?0.01 – 0.03, I² = 0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99–1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72–1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85–1.01) when compared with the placebo.ConclusionAnti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.     

Increased circulating interleukin-6 (IL-6) activity in endotoxin-challenged mice pretreated with anti-IL-6 antibody is due to IL-6 accumulated in antigen-antibody complexes

Mice pretreated with monoclonal anti-interleukin-6 (IL-6) antibody and then challenged with lipopolysaccharide (LPS), paradoxically develop higher levels of circulating biological IL-6 activity, as measured by the hybridoma growth promotion assay, than mice similarly challenged but not pretreated with antibody. Here we provide evidence that this increased biological activity was entirely accounted for by the presence of increased amounts of IL-6 protein, which could be isolated by immunoaffinity chromatography and subsequently visualized after gel electrophoresis. Chromatography on a protein G matrix and a sandwich ELISA allowed to demonstrate that all IL-6 present in the serum was in the form of antigen-antibody complexes. Serum samples of antibody-treated animals which contained the highest biological activity typically contained near equimolar concentrations of IL-6 and antibody. In vitro neutralization tests with pure antibody and IL-6 demonstrated that, with both antibodies tested, more than 1000-fold molar excess of antibody is needed for neutralization in the hybridoma growth assay. It is concluded that increased biological activity in serum of the anti-IL-6 antibody-treated mice is due to sequestration of the endogenous IL-6 in the form of antigen-antibody complexes which, due to the lack of sufficient antibody excess, produce nearly full activity in the hybridoma growth assay.     

Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis

BackgroundLatent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA).ObjectivesConsidering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients.Study designUnspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls.ResultsDespite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA.DiscussionCMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients.     

Administration of neutralizing antibody against rabbit IL-1 receptor antagonist exacerbates lipopolysaccharide-induced arthritis in rabbits

Endogenous IL-1 receptor antagonist (IL-1ra) may down-regulate part of IL-1 actions. We examined the participation of endogenous IL-1ra in the production of IL-1 in vitro. Macrophages cultured on adherent IgG produced a 100-fold molar excess of IL-1ra, compared with IL-1. In the presence of a neutralizing monoclonal antibody (mAb) against rabbit IL-1ra, the production of antigenic IL-1 increased by 20–60%. Since the molar ratio of IL-1ra over IL-1 was 160- to 400-fold in synovial fluid (SF) of lipopolysaccharide (LPS)-induced arthritis, we examined the functional role of endogenous IL-1ra in the regulation of inflammatory responses. When measured in the presence of anti-IL-1ra mAb, masked IL-1 activity in SF became evident, with a 3- to 4-fold increment. The administration of anti-IL-1ra mAb with LPS into rabbit knee joints increased the IL-1 activity 4-fold and the production of antigenic IL-1 by 30–50%. The treatment also enhanced by 20–40% LPS-induced leukocyte infiltration and protein leakage. Therefore, endogenous IL-1ra apparently acts as a down-regulating factor for limiting delecterious effects of IL-1 by masking the biological activity and by inhibiting the production.accepted by M. Katori     

Binding Sites of Interleukin-3-Mimetic Monoclonal Autoantibodies Derived from a MRL/lpr Mouse

MRL/lpr mouse-derived interleukin-3 (IL-3)-mimetic monoclonal antibodies were examined for their binding sites. One of these five antibodies (B10, F8, F9, F12, H 11), F9 interacted with the IL-3 receptor, as if it were an anti-idiotypic antibody; the IL-3-mimetic activity of F9 was blocked by a neutralizing rat monoclonal anti-IL-3 antibody. IL-3 mRNA was not detected in hybridoma F9, as analyzed by the SI protection assay, Thus, the activity neutralized by the rat antibody is of the F9 antibody itself but not the IL-3 type. Such blocking was not observed with the IL-3-mimetic activity of the other MRL/lpr-derived monoclonal antibodies. On the other hand, the binding of all these monoclonal antibodies to IL-3-depen-dent cells was inhibited by each other and vice versa, as analyzed by two-color flow cytometry. This indicates that the binding sites of the five monoclonal antibodies are located so close to each other that the binding of one would interfere with the binding of any one of the others (since the binding experiment was done on ice, it is unlikely that the inhibition is due to down-modulation of the receptors). Taken together the results obtained by the enzyme digestion study, we discussed that all five IL-3-mimetic monoclonal antibodies are directed to the IL-3 receptor, but only F9 binds to the portion directly responsible for the binding of IL-3 and the other antibodies (B10, F8, F12, H11) bind to different portions, respectively, which are adjacent or overlapping to the binding site of F9.     

Aging in COVID-19: Vulnerability,immunity and intervention

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic was first reported in Wuhan, China in December 2019, moved across the globe at an unprecedented speed, and is having a profound and yet still unfolding health and socioeconomic impacts. SARS-CoV-2, a β-coronavirus, is a highly contagious respiratory pathogen that causes a disease that has been termed the 2019 coronavirus disease (COVID-19). Clinical experience thus far indicates that COVID-19 is highly heterogeneous, ranging from being asymptomatic and mild to severe and causing death. Host factors including age, sex, and comorbid conditions are key determinants of disease severity and progression. Aging itself is a prominent risk factor for severe disease and death from COVID-19. We hypothesize that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults. Much remains to be learned about the immune responses to SARS-CoV-2 infection. We need to begin partitioning all immunological outcome data by age to better understand disease heterogeneity and aging. Such knowledge is critical not only for understanding of COVID-19 pathogenesis but also for COVID-19 vaccine development.     

Pseudo-trisomy 13 syndrome

We have coined the term “pseudo-trisomy 13 syndrome” to designate cases of holoprosencephaly, severe facial anomalies, postaxial polydactyly, various other congenital defects, and normal chromosomes. Eleven instances are summarized. Two pairs of sibs and two other cases with consanguinity suggest autosomal recessive inheritance. Autosomal recessive inheritance is possible. Alternately, an undetected microdeletion and etiologic heterogeneity (some cases possibly representing dominant new mutations) must be considered. Further delineation is necessary. It is hoped that this paper will serve as a focus for further discussion of the problem.     

Preliminary definition of a “critical region” of chromosome 13 in q32: Report of 14 cases with 13q deletions and review of the literature

We report on 14 patients with partial deletions of chromosome 13q. These patients exhibit a wide spectrum of phenotypes. Deletions limited to proximal bands q13–q31 are associated with growth retardation but not with major malformations. We review the literature since 1975 and summarize 13q deletion cases which have a phenotype involving one or more major malformations and mental retardation. Analysis of the breakpoints of these cases, as well as those reported by us, supports the hypothesis that only deletions involving at least part of band q32 are associated with major malformations and digital abnormalities. Patients with more distal deletions have severe mental retardation but do not have major malformations or growth retardation. A group of patients in whom the breakpoint is stated to be within q32 has had an intermediate phenotype. This suggests that it may be possible to define subregions within q32 whose deletion is associated with particular developmental defects. © 1993 Wiley-Liss, Inc.     

Molecular and cytogenetic characterisation of an unusual case of partial trisomy/partial monosomy 13 mosaicism: 46,XX,r(13)(p11q14)/46,XX,der(13)t(13;13)(q10;q14)

A female infant with multiple malformations and mental retardation was noted to have a rare de novo chromosome abnormality involving mosaicism with two cell lines, one with a ring chromosome 13, and the other with partial trisomy 13 owing to a complex rearrangement. Cytogenetic examination excluded the presence of a t(13q;13q) cell line and showed a cell line with a marker chromosome containing two chromosome 13 long arms joined together after deletion of a part (q11→q14) of one of them. In addition, the absence of a cell line with two normal chromosomes 13 or a cell line with a t(13q;13q) implies that the ring (13) and the marker (13) arose from a single event at the first cleavage division.
The two cell lines were present in different proportions in both peripheral blood lymphocytes and skin fibroblasts. The results of microsatellite characterisation clearly indicate the paternal origin and the absence of recombination, supporting the postzygotic origin of both the ring and the marker chromosome.


Keywords: unusual mosaicism; ring 13; partial trisomy 13; partial monosomy 13     

Evidence for a critical region for penoscrotal inversion,hypospadias, and imperforate anus within chromosomal region 13q32.2q34

Two unrelated patients with small distal deletions of the long arm of chromosome 13 are described, with shawl scrotum and penoscrotal transposition, penoscrotal hypospadias, a reduced perineum, and anal atresia. The patients have small deletions of 13(q32.2qter) and 13(q32q34), respectively. This report and the literature present evidence for one or possibly more gene(s) within region 13q32.2q34 which regulate the development of the ano-genital structures. The clinical spectrum includes bifid or shawl scrotum, hypospadias, biseptate uterus, malplaced and imperforate anus, and common cloaca. © 1996 Wiley-Liss, Inc.     

IL-13和变态反应

IL-13是一种具有高度多向性的Th2细胞因子 ,它与IL 4在结构和功能上有许多相似之处。IL 13通过对单核 /巨噬细胞、内皮细胞、B细胞和嗜酸性粒细胞的调节作用而参与变态反应。最近许多研究表明 ,IL 13在变态反应过程中起着独特而重要的作用。本文对IL 13的分子生物学和在变态反应中的作用机制进行综述。随着研究的深入 ,IL 13可能在变态反应性疾病的治疗中具有广阔的应用前景。     

氨基比林呼气试验的临床应用现状和问题

13C呼气试验检测肝脏储备功能在短时间内得到研究者的认同，这不仅因为其非侵害性，更是由于从某种程度上它具有较高的灵敏度、特异度以及简便、可重复的特性。相比于传统的血清学检查和定量肝功能动态检查，临床上的肝储备功能定量检测更倾向于采用这种安全无创的手段。     

059 IL-13与支气管哮喘

支气管哮喘是由多种细胞特别是肥大细胞、嗜酸性粒细胞和T淋巴细胞参与的慢性气道炎症.哮喘的发生过程中有多种细胞因子参与,白介素-13(IL-13)是近年来新克隆的淋巴因子.IL-13作为Th2型细胞因子成员,具有多种生物学功能.通过激活嗜酸性粒细胞,减少其凋亡,促进IgE分泌等机制,参与哮喘炎症的维持,诱导气道高反应性及小气道结构重建.     

IL-13中和抗体对哮喘小鼠恢复期气道炎症及Th1/Th2功能的影响

目的 探讨白细胞介素13（IL-13）中和抗体对哮喘小鼠恢复期气道炎症及Th1／Th2功能的影响。方法Balb/c小鼠24只,随机分为3组,即对照组、模型组、治疗组。模型组和治疗组用鸡卵清蛋白（0VA）致敏和激发,建立哮喘小鼠模型,对照组用生理盐水代替OVA。治疗组自最后一次激发后24h起,每48h注射IL-13中和抗体1次,连续14d,对照组和模型组则用生理盐水替代。结果治疗组肺组织病理切片较模型组相比,炎症细胞明显减少,肺气肿程度明显减轻。血清及支气管肺泡灌洗液（BALF）中,治疗组较模型组IL-4、OVA特异性IgE明显下降,IFN-γ明显增加,基本接近正常对照组。结论IL-13中和抗体对哮喘小鼠恢复期有明显的治疗作用,除能明显减轻气道炎症和肺气肿外,还能纠正哮喘小鼠体内存在的Th1／Th2细胞因子失调。     

乙型肝炎患者血清IL-13和PGE1含量的检测及其意义

目的：通过检测乙型肝炎患者和正常对照组血清中IL-13和PGE1的水平及其与ALT、AST的相关性，探讨Ⅰ型超敏反应与乙型肝炎免疫学发病机制的关系。方法：应用酶联免疫吸附实验-双抗体夹心法，检测50例急、慢性乙型肝炎及35例正常对照组血清IL-13和PGE1水平，并观察与血清中ALT及AST水平的相关性。结果：①10例急性乙型肝炎患者血清中IL-13和PGE1含量明显高于对照组；②35例慢性乙型肝炎患者血清中IL-13和PGE1含量明显高于对照组，其中慢性重度组升高最明显，其次为中度组和轻度组；③IL-13和PGE1水平与血清ALT、AST含量均呈显著的正相关关系。结论：乙型肝炎患者血清中IL-13和PGE1水平的高低，可反映肝组织的损害程度，对病情和预后的判定也有一定的参考价值。     

070 IL-13在哮喘中的作用

支气管哮喘是以Th2型细胞因子增高和气道高反应性为特征的变态反应性疾病.白细胞介素-13(IL-13)是近年来新克隆的Th2型细胞因子,它通过诱导B细胞增殖和分化,促进IgE合成,活化嗜酸性粒细胞,延长嗜酸性粒细胞的存活,诱导气道高反应性等机制,在哮喘的发生中起重要的作用.