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Structural and Functional Characterization of Medicinal Plants as Selective Antibodies towards Therapy of COVID-19 Symptoms. 药用植物作为治疗 COVID-19 症状的选择性抗体的结构和功能特征。
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-05-07 DOI: 10.3390/antib13020038
Fatemeh Mollaamin

Considering the COVID-19 pandemic, this research aims to investigate some herbs as probable therapies for this disease. Achillea millefolium (Yarrow), Alkanet, Rumex patientia (Patience dock), Dill, Tarragon, and sweet fennel, including some principal chemical compounds of achillin, alkannin, cuminaldehyde, dillapiole, estragole, and fenchone have been selected. The possible roles of these medicinal plants in COVID-19 treatment have been investigated through quantum sensing methods. The formation of hydrogen bonding between the principal substances selected in anti-COVID natural drugs and Tyr-Met-His (the database amino acids fragment), as the active area of the COVID protein, has been evaluated. The physical and chemical attributes of nuclear magnetic resonance, vibrational frequency, the highest occupied molecular orbital energy and the lowest unoccupied molecular orbital energy, partial charges, and spin density have been investigated using the DFT/TD-DFT method and 6-311+G (2d,p) basis set by the Gaussian 16 revision C.01 program toward the industry of drug design. This research has exhibited that there is relative agreement among the results that these medicinal plants could be efficient against COVID-19 symptoms.

考虑到 COVID-19 的流行,本研究旨在调查一些草药作为该疾病的可能疗法。研究选取了蓍草、阿尔卡内特、忍冬、莳萝、龙蒿和甜茴香,包括一些主要的化学成分:苦味素、鞣质素、积雪草醛、莳萝酚、雌甾醇和茴香酮。通过量子传感方法研究了这些药用植物在 COVID-19 治疗中可能发挥的作用。评估了抗 COVID 天然药物中选定的主要物质与作为 COVID 蛋白活性区的 Tyr-Met-His(数据库氨基酸片段)之间形成氢键的情况。研究采用 DFT/TD-DFT 方法和 6-311+G (2d,p) 基集,通过 Gaussian 16 revision C.01 程序对核磁共振、振动频率、最高占有分子轨道能和最低未占有分子轨道能、偏电荷和自旋密度等物理和化学属性进行了研究,并将其应用于药物设计行业。研究结果表明,这些药用植物对 COVID-19 症状有较好的疗效。
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引用次数: 0
Case Series: Efficacy of Polyclonal Intravenous Immunoglobulin for Refractory Clostridioides difficile Infection. 病例系列:多克隆静脉注射免疫球蛋白治疗难治性艰难梭菌感染的疗效。
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-04-01 DOI: 10.3390/antib13020026
Sophie A Ragan, Caitlin Doyle, Neha Datta, Heather Abdic, Mark H Wilcox, Ros Montgomery, Shanika A Crusz, Yashwant R Mahida, Tanya M Monaghan

Background: Intravenous immunoglobulin (IVIg) for Clostridioides difficile infection (CDI) no longer features in treatment guidelines. However, IVIg is still used by some clinicians for severe or recurrent CDI (rCDI) cases. The main objective of this study was to investigate the efficacy of IVIg and to identify possible predictors of disease resolution post IVIg administration for patients with CDI.

Methods: This retrospective observational cohort study of patients ≥2 years old hospitalised with severe, relapsing, or rCDI treated with IVIg therapy was performed in a large UK tertiary hospital between April 2018 and March 2023. Scanned electronic notes from patient admissions and clinical reporting systems were used to collect relevant data.

Results: In total, 20/978 patients diagnosed with CDI over the 5-year study were treated with IVIg. Twelve (60%) had hospital-onset CDI. Eleven of the twenty patients (55%) responded to treatment, with a mean of 8.6 (SD 10.7) days to disease resolution. Sixteen (80%) patients were treated for severe CDI and four (20%) for rCDI (n = 3) and relapsing CDI (n = 1). There were no statistically significant differences in possible independent predictors of disease resolution post IVIg administration between groups. There was an average of 6.2 (4.9) days to IVIg administration after diagnosis with no difference between responders and non-responders (p = 0.88) and no further significant difference in additional indicators. Four (36%) of the responders were immunosuppressed compared to just one (11%) of the non-responders (p = 0.15). Six of the responders (two with recurrent and four with severe CDI) improved rapidly within 2 days, and three of these were immunosuppressed.

Conclusion: We observed disease resolution post IVIg therapy in over 50% of patients with refractory CDI. Our data also support a potential enhanced effect of IVIg in immunosuppressed individuals. Thus, the role of IVIg for CDI treatment, particularly in the immunosuppressed, warrants future case-control studies coupled to mechanistic investigations to improve care for this ongoing significant healthcare-associated infection.

背景:治疗艰难梭菌感染(CDI)的静脉注射免疫球蛋白(IVIg)已不再列入治疗指南。然而,一些临床医生仍在对严重或复发性 CDI(rCDI)病例使用 IVIg。本研究的主要目的是探讨IVIg的疗效,并确定CDI患者使用IVIg后疾病缓解的可能预测因素:这项回顾性观察队列研究于 2018 年 4 月至 2023 年 3 月期间在英国一家大型三甲医院进行,研究对象为住院治疗的≥2 岁重症、复发性或 rCDI 患者,这些患者均接受过 IVIg 治疗。通过扫描患者入院电子记录和临床报告系统收集相关数据:在为期5年的研究中,共有20/978名确诊为CDI的患者接受了IVIg治疗。其中 12 例(60%)是在医院发病的 CDI 患者。20名患者中有11名(55%)对治疗有反应,平均8.6天(标准差10.7天)疾病缓解。16名患者(80%)接受了重症CDI治疗,4名患者(20%)接受了rCDI(3人)和复发性CDI(1人)治疗。两组患者在使用 IVIg 后疾病缓解的可能独立预测因素方面没有明显的统计学差异。确诊后平均 6.2(4.9)天开始使用 IVIg,应答者与非应答者之间无差异(P = 0.88),其他指标也无明显差异。四名应答者(36%)有免疫抑制,而无应答者中仅有一人(11%)有免疫抑制(p = 0.15)。六名应答者(两名复发性 CDI 患者和四名重症 CDI 患者)的病情在两天内迅速好转,其中三人患有免疫抑制:结论:我们观察到 50%以上的难治性 CDI 患者在接受 IVIg 治疗后病情得到缓解。我们的数据还证明,IVIg 对免疫抑制患者的作用可能会增强。因此,IVIg 在 CDI 治疗中的作用,尤其是在免疫抑制人群中的作用,值得在未来开展病例对照研究,并进行机理调查,以改善对这一持续存在的重大医疗相关感染的治疗。
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引用次数: 0
Anti-CD99 Antibody Therapy Triggers Macrophage-Dependent Ewing Cell Death In Vitro and Myeloid Cell Recruitment In Vivo. 抗 CD99 抗体疗法在体外引发巨噬细胞依赖性尤文细胞死亡,在体内引发髓系细胞募集。
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-03-18 DOI: 10.3390/antib13010024
Allison F O'Neill, Evelyn M Nguyen, Evelyn D Maldonado, Matthew R Chang, Jiusong Sun, Quan Zhu, Wayne A Marasco

Background: Ewing sarcoma is a rare tumor of the bone or soft tissues characterized by diffuse membranous staining for CD99. As this tumor remains incurable in the metastatic, relapsed, and refractory settings, we explored the downstream immune implications of targeting CD99.

Methods: We discovered a human anti-CD99 antibody (NOA2) by phagemid panning and investigated NOA2 immune cell-mediated cytotoxicity in vitro and in vivo focusing on the myeloid cell compartment, given that M2 macrophages are present in human tumors and associated with a poor prognosis.

Results: NOA2 is capable of inducing immune effector cell-mediated Ewing death in vitro via engagement of macrophages. Mice with metastatic Ewing tumors, treated with NOA2, experience tumor growth arrest and an associated increase in intratumoral macrophages. Further, incubation of macrophages and Ewing cells with NOA2, in conjunction with anti-PILRα antibody blockade in vitro, results in the reactivation of previously dormant macrophages possibly due to interrupted binding of Ewing CD99 to macrophage PILRα.

Conclusions: These studies are the first to demonstrate the role of human immune effector cells in anti-CD99-mediated Ewing tumor death. We propose that the engagement of CD99 by NOA2 results in the recruitment of intratumoral macrophages. In addition, interruption of the CD99:PILRα checkpoint axis may be a relevant therapeutic approach to activate tumor-associated macrophages.

背景:尤文肉瘤是一种罕见的骨或软组织肿瘤,其特点是CD99弥漫膜性染色。由于这种肿瘤在转移、复发和难治的情况下仍无法治愈,我们探索了靶向 CD99 的下游免疫影响:方法:我们通过噬菌体平移发现了一种人类抗 CD99 抗体(NOA2),并研究了 NOA2 在体外和体内由免疫细胞介导的细胞毒性,重点是髓细胞区系,因为 M2 巨噬细胞存在于人类肿瘤中,并与不良预后相关:结果:NOA2能够通过巨噬细胞的参与,在体外诱导免疫效应细胞介导的尤文死亡。转移性尤文肿瘤小鼠经 NOA2 治疗后,肿瘤生长停止,瘤内巨噬细胞随之增加。此外,在体外用 NOA2 与抗 PILRα 抗体阻断一起孵育巨噬细胞和尤文细胞,可能由于尤文 CD99 与巨噬细胞 PILRα 的结合中断,导致先前休眠的巨噬细胞重新活化:这些研究首次证明了人类免疫效应细胞在抗 CD99 介导的尤文肿瘤死亡中的作用。我们认为,NOA2 与 CD99 的接合导致了瘤内巨噬细胞的招募。此外,干扰 CD99:PILRα 检查点轴可能是激活肿瘤相关巨噬细胞的一种相关治疗方法。
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引用次数: 0
Episomal Vectors for Stable Production of Recombinant Proteins and Engineered Antibodies. 用于稳定生产重组蛋白质和工程抗体的外显子载体。
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-03-11 DOI: 10.3390/antib13010018
Ian Fallahee, Daniel Hawiger

There is tremendous interest in the production of recombinant proteins, particularly bispecific antibodies and antibody-drug conjugates for research and therapeutic use. Here, we demonstrate a highly versatile plasmid system that allows the rapid generation of stable Expi293 cell pools by episomal retention of transfected DNA. By linking protein expression to puromycin resistance through an attenuated internal ribosome entry site, we achieve stable cell pools producing proteins of interest. In addition, split intein-split puromycin-mediated selection of two separate protein expression cassettes allows the stable production of bispecific antibody-like molecules or antibodies with distinct C-terminal heavy chain modifications, such as an antigen on one chain and a sortase tag on the other chain. We also use this novel expression system to generate stable Expi293 cell pools that secrete sortase A Δ59 variant Srt4M. Using these reagents, we prepared a site-specific drug-to-antibody ratio of 1 antibody-siRNA conjugate. We anticipate the simple, robust, and rapid stable protein expression systems described here being useful for a wide variety of applications.

人们对生产重组蛋白,特别是用于研究和治疗的双特异性抗体和抗体-药物共轭物有着极大的兴趣。在这里,我们展示了一种通用性很强的质粒系统,它能通过外显子保留转染 DNA 快速生成稳定的 Expi293 细胞池。通过一个减弱的内部核糖体进入位点将蛋白质表达与嘌呤霉素抗性联系起来,我们实现了产生感兴趣蛋白质的稳定细胞池。此外,通过嘌呤霉素介导的两个独立蛋白表达盒的分离内含体-分离嘌呤霉素选择,可以稳定地生产双特异性抗体样分子或具有不同 C 端重链修饰的抗体,如一条链上的抗原和另一条链上的分类酶标签。我们还利用这种新型表达系统生成了稳定的 Expi293 细胞池,它们能分泌分选酶 A Δ59 变体 Srt4M。利用这些试剂,我们制备了一种位点特异性药物抗体比为 1 的抗体-siRNA 结合物。我们预计,这里描述的简单、稳健、快速的稳定蛋白质表达系统可用于多种应用。
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引用次数: 0
Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development. 炎症性肠病患者生物疗法的免疫原性和抗药性抗体发展导致的疗效丧失。
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-02-26 DOI: 10.3390/antib13010016
Tsvetelina Velikova, Metodija Sekulovski, Monika Peshevska-Sekulovska

Many patients with inflammatory bowel disease (IBD) experience a loss of effectiveness to biologic therapy (i.e., anti-TNF therapy, etc.). Therefore, in addition to the adverse effects of the treatment, these patients also face failure to achieve and maintain remission. Immunogenicity, the process of production of antibodies to biological agents, is fundamental to the evolution of loss of response to treatment in IBD patients. The presence of these antibodies in patients is linked to decreased serum drug levels and inhibited biological activity. However, immunogenicity rates exhibit significant variability across inflammatory disease states, immunoassay formats, and time periods. In this review, we aimed to elucidate the immunogenicity and immune mechanisms of antibody formation to biologics, the loss of therapy response, clinical results of biological treatment for IBD from systematic reviews and meta-analyses, as well as to summarize the most recent strategies for overcoming immunogenicity and approaches for managing treatment failure in IBD.

许多炎症性肠病(IBD)患者在接受生物疗法(即抗肿瘤坏死因子疗法等)后都会失去疗效。因此,除了治疗的不良反应外,这些患者还面临着无法实现和维持缓解的问题。免疫原性,即对生物制剂产生抗体的过程,是导致 IBD 患者对治疗失去反应的根本原因。患者体内出现这些抗体与血清药物水平下降和生物活性受抑制有关。然而,免疫原性率在不同的炎症疾病状态、免疫测定格式和时间段中表现出显著的差异性。在这篇综述中,我们旨在从系统综述和荟萃分析中阐明生物制剂的免疫原性和抗体形成的免疫机制、治疗反应的丧失、生物制剂治疗 IBD 的临床结果,并总结克服免疫原性的最新策略和处理 IBD 治疗失败的方法。
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引用次数: 0
Development of a Bispecific IgG1 Antibody Targeting BCMA and PDL1. 开发靶向 BCMA 和 PDL1 的双特异性 IgG1 抗体
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-02-20 DOI: 10.3390/antib13010015
Irene Cattaneo, Sylvie Choblet, Rut Valgardsdottir, Muriel Roth, Annamaria Massafra, Marten Beeg, Marco Gobbi, Martine Duonor-Cerutti, Josée Golay

We designed, produced, and purified a novel IgG1-like, bispecific antibody (bsAb) directed against B-cell maturation antigen (BCMA), expressed by multiple myeloma (MM) cells, and an immune checkpoint inhibitor (ICI), PDL1, expressed in the MM microenvironment. The BCMA×PDL1 bsAb was fully characterized in vitro. BCMA×PDL1 bound specifically and simultaneously, with nM affinity, to both native membrane-bound antigens and to the recombinant soluble antigen fragments, as shown by immunophenotyping analyses and surface plasmon resonance (SPR), respectively. The binding affinity of bsAb for PDL1 and BCMA was similar to each other, but PDL1 affinity was about 10-fold lower in the bsAb compared to parent mAb, probably due to the steric hindrance associated with the more internal anti-PDL1 Fab. The bsAb was also able to functionally block both antigen targets with IC50 in the nM range. The bsAb Fc was functional, inducing human-complement-dependent cytotoxicity as well as ADCC by NK cells in 24 h killing assays. Finally, BCMA×PDL1 was effective in 7-day killing assays with peripheral blood mononuclear cells as effectors, inducing up to 75% of target MM cell line killing at a physiologically attainable, 6 nM, concentration. These data provide the necessary basis for future optimization and in vivo testing of this novel bsAb.

我们设计、生产并纯化了一种新型 IgG1 样双特异性抗体(bsAb),这种抗体针对多发性骨髓瘤(MM)细胞表达的 B 细胞成熟抗原(BCMA)和 MM 微环境中表达的免疫检查点抑制剂(ICI)PDL1。BCMA×PDL1 bsAb 在体外进行了全面鉴定。免疫分型分析和表面等离子体共振(SPR)分别显示,BCMA×PDL1以nM的亲和力同时与原生膜结合抗原和重组可溶性抗原片段特异性结合。bsAb 与 PDL1 和 BCMA 的结合亲和力相似,但与母体 mAb 相比,bsAb 与 PDL1 的亲和力低约 10 倍,这可能是由于内部抗 PDL1 Fab 的立体阻碍作用所致。bsAb 还能对两个抗原靶点进行功能性阻断,IC50 在 nM 范围内。该 bsAb Fc 具有功能性,可诱导人体补体依赖性细胞毒性,并在 24 小时杀伤试验中诱导 NK 细胞的 ADCC。最后,BCMA×PDL1 在以外周血单核细胞为效应物的 7 天杀伤试验中非常有效,在生理浓度为 6 nM 的情况下可诱导高达 75% 的靶 MM 细胞系死亡。这些数据为这种新型 bsAb 今后的优化和体内测试提供了必要的依据。
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引用次数: 0
Diversity in the HLA-I Recognition of HLA-F Monoclonal Antibodies: HLA-F or HLA-Ib Monospecific, HLA-E or HLA-G Bispecific Antibodies with or without HLA-Ia Reactivity. HLA-F 单克隆抗体识别 HLA-I 的多样性:HLA-F 或 HLA-Ib 单特异性抗体、HLA-E 或 HLA-G 双特异性抗体与或不与 HLA-Ia 反应。
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-01-31 DOI: 10.3390/antib13010008
Mepur H Ravindranath, Narendranath M Ravindranath, Carly J Amato-Menker, Fatiha El Hilali, Edward J Filippone

Previous investigators have used various anti-HLA-F monoclonal antibodies (mAbs) to demonstrate that the tissue distribution of HLA-F is highly restricted. Notably, these mAbs differed in their immunodiagnostic capabilities. Specifically, mAbs Fpep1.1 and FG1 detected HLA-F intracellularly in B cells but not on the cell surface, whereas mAb 3D11 detected HLA-F on the cell surface. The presence of HLA-F on T cells was recognized by mAb FG1 but not by mAb Fpep1.1. mAb 3D11 detected HLA-F on the cell surface of activated B cells and on peripheral blood lymphocytes, but not on the normal cells. Importantly, mAb 3D11 revealed that HLA-F exists as a heavy chain (HC) monomer, rather than as an HC associated with B2m. Although these mAbs are believed to be specific to HLA-F, their monospecificity has not been formally established, which is critical for immunodiagnostic and therapeutic purposes. Previously, we investigated the diversity of HLA class I reactivities of anti-HLA-E mAbs using HLA-I coated multiplex bead assays on a Luminex platform. We reported that more than 80% of the HLA-E mAbs were cross-reactive with other HLA-I molecules, with exceptionally few truly HLA-E-monospecific mAbs. In the present investigation, we generated IgG mAbs against HCs of HLA-F in Balb/C mice and examined the cross-reactivity of anti-HLA-F mAbs with other HLA-I alleles using a multiplex bead assay on the Luminex platform. Beads coated with an array of HLA homo- and heterodimers of different HLA-Ia (HLA-A, HLA-B, and HLA-C) and Ib (HLA-E, HLA-F, and HLA-G) alleles were used to examine the binding of the anti-HLA-F mAbs. Only two mAbs were HLA-F monospecific, and five were HLA-Ib restricted. Several anti-HLA-F mAbs cross-reacted with HLA-E (n = 4), HLA-G (n = 3), HLA-Ia alleles (n = 9), HLA-G and HLA-Ia (n = 2), and HLA-Ib and HLA-Ia (n = 6). This monospecificity and polyreactivity were corroborated by the presence of HLA-F monospecific and HLA-I-shared sequences. This study emphasizes the need to monitor the mono-specificity of HLA-F for reliable immunodiagnostics and passive immunotherapy.

以前的研究人员曾使用各种抗 HLA-F 单克隆抗体(mAbs)来证明 HLA-F 的组织分布高度受限。值得注意的是,这些 mAbs 的免疫诊断能力各不相同。具体来说,mAbs Fpep1.1 和 FG1 能检测到 B 细胞内的 HLA-F,但不能检测到细胞表面的 HLA-F,而 mAb 3D11 则能检测到细胞表面的 HLA-F。mAb 3D11 能检测到活化 B 细胞和外周血淋巴细胞表面的 HLA-F,但不能检测到正常细胞表面的 HLA-F。重要的是,mAb 3D11 发现 HLA-F 是作为重链 (HC) 单体存在,而不是作为与 B2m 相关的 HC 存在。虽然这些 mAb 被认为对 HLA-F 具有特异性,但它们的单特异性尚未正式确定,而这对免疫诊断和治疗目的至关重要。此前,我们在 Luminex 平台上使用 HLA-I 包被的多重检测珠检测了抗 HLA-E mAbs 的 HLA I 类反应活性的多样性。我们发现 80% 以上的 HLA-E mAbs 与其他 HLA-I 分子有交叉反应,真正的 HLA-E 单特异性 mAbs 极少。在本研究中,我们在 Balb/C 小鼠体内生成了抗 HLA-F HCs 的 IgG mAbs,并使用 Luminex 平台上的多重微珠检测法检测了抗 HLA-F mAbs 与其他 HLA-I 等位基因的交叉反应。在检测抗 HLA-F mAbs 的结合力时,使用了涂有不同 HLA-Ia 等位基因(HLA-A、HLA-B 和 HLA-C)和 Ib 等位基因(HLA-E、HLA-F 和 HLA-G)的 HLA 同二聚体和异二聚体阵列的微珠。只有两种 mAbs 是 HLA-F 单特异性的,五种受 HLA-Ib 限制。几种抗 HLA-F mAbs 与 HLA-E(n = 4)、HLA-G(n = 3)、HLA-Ia 等位基因(n = 9)、HLA-G 和 HLA-Ia (n = 2)以及 HLA-Ib 和 HLA-Ia (n = 6)发生交叉反应。HLA-F单特异性和HLA-I共享序列的存在证实了这种单特异性和多反应性。这项研究强调了监测 HLA-F 的单特异性以进行可靠的免疫诊断和被动免疫治疗的必要性。
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引用次数: 0
Immune Responses to Anti-Hepatitis C Virus Antibodies during Pre-Liver Transplantation Direct-Acting Antiviral Therapy in Hepatitis C Virus-Infected Recipients Associated with Post-Liver Transplantation Allograft Injury. 丙型肝炎病毒感染受者肝移植前直接作用抗病毒疗法期间抗丙型肝炎病毒抗体的免疫反应与肝移植后同种异体移植损伤相关。
IF 3 Q3 IMMUNOLOGY Pub Date : 2024-01-16 DOI: 10.3390/antib13010007
Shu-Hsien Lin, Kun-Ta Wu, Chih-Chi Wang, Kuang-Tzu Huang, Li-Wen Hsu, Hock-Liew Eng, King-Wah Chiu

Background and aims: The impact of antibody responses following direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined.

Methods: In this observational cohort study, we aimed to explore the association between changes in anti-HCV antibody titers following pre-LT DAA therapy and allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR).

Results: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (the DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (the DAA-naïve group). A higher incidence of post-LT BCs was observed in the DAA group (p = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (p = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (p < 0.005).

Conclusions: In conclusion, we speculate that the upregulation of anti-HCV antibody titers, which might have been induced via the restoration of HCV-specific immune responses through pre-LT DAA therapy, was associated with post-LT allograft injury.

背景和目的:肝移植(LT)前后,丙型肝炎病毒(HCV)感染者接受直接作用抗病毒(DAA)治疗后抗体反应的影响仍未确定:在这项观察性队列研究中,我们旨在探讨肝移植前DAA治疗后抗HCV抗体滴度的变化与异体移植损伤(包括胆道并发症(BCs)和急性细胞排斥反应(ACR))之间的关联:结果:2015年1月至2021年2月期间共纳入153例病例。在LT前后(第30天)评估了血清抗HCV抗体滴度。在所有受者中,31/153(20.3%)在LT前接受了DAA治疗(DAA组),122/153(79.7%)在LT前未接受DAA治疗(DAA未接受组)。在 DAA 组中观察到 LT 后 BC 的发生率更高(p = 0.028)。与DAA无效组相比,DAA组的抗HCV滴度平均上调水平显著更高(p = 0.0024);此外,在出现BCs(n = 28)和ACR(n = 41)的受者中,DAA组的抗HCV抗体滴度平均上调水平显著更高(p < 0.005):总之,我们推测抗HCV抗体滴度的上调可能是通过LT前的DAA治疗恢复HCV特异性免疫反应而诱导的,与LT后的异体移植损伤有关。
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引用次数: 0
Is It Time to Reconsider Rituximab Dosing Regimens for Pemphigus Vulgaris? 是时候重新考虑治疗大疱性类天疱疮的利妥昔单抗剂量方案了吗?
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-01-05 DOI: 10.3390/antib13010004
Christian Ciolfi, Jacopo Tartaglia, Mauro Alaibac
Rituximab is currently approved for patients affected by moderate-to-severe pemphigus vulgaris, a severe autoimmune blistering skin disease that can be life-threatening. The standard rituximab dosing regimens, originally established for B-cell non-Hodgkin’s lymphomas, have been recognized to exceed the effective dose required for inducing B-cell depletion, considering that the B-cell burden in pemphigus vulgaris is considerably lower than in lymphoproliferative disorders. We herein report our experience with very ultra-low-dose rituximab in two patients affected by pemphigus vulgaris.
利妥昔单抗目前被批准用于治疗中重度寻常性天疱疮患者,这是一种严重的自身免疫性大疱性皮肤病,可危及生命。利妥昔单抗的标准剂量方案最初是为 B 细胞非霍奇金淋巴瘤制定的,但考虑到寻常型天疱疮的 B 细胞负担远低于淋巴组织增生性疾病,该方案被认为超出了诱导 B 细胞耗竭所需的有效剂量。我们在此报告两名寻常型丘疹性荨麻疹患者使用超低剂量利妥昔单抗的经验。
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引用次数: 0
Clinical and Analytical Performance of ELISA Salivary Serologic Assay to Detect SARS-CoV-2 IgG in Children and Adults 检测儿童和成人 SARS-CoV-2 IgG 的 ELISA 唾液血清学测定的临床和分析性能
IF 4.7 Q3 IMMUNOLOGY Pub Date : 2024-01-05 DOI: 10.3390/antib13010006
Andrea Padoan, C. Cosma, C. di Chiara, Giulia Furlan, Stefano Gastaldo, Ilaria Talli, Daniele Donà, Daniela Basso, Carlo Giaquinto, Mario Plebani
Saliva is a promising matrix with several purposes. Our aim is to verify if salivary anti-SARS-CoV-2 antibody determination is suitable for monitoring immune responses. One hundred eighty-seven subjects were enrolled at University-Hospital Padova: 105 females (56.1%) and 82 males (43.9%), 95 (50.8%) children and 92 (49.2%) adults. Subjects self-collected saliva using Salivette; nineteen subjects collected three different samples within the day. A serum sample was obtained for all individuals. The N/S anti-SARS-CoV-2 salivary IgG (sal-IgG) and serum anti-SARS-CoV-2 S-RBD IgG (ser-IgG) were used for determining anti-SARS-CoV-2 antibodies. The mean (min–max) age was 9.0 (1–18) for children and 42.5 (20–61) for adults. Of 187 samples, 63 were negative for sal-IgG (33.7%), while 7 were negative for ser-IgG (3.7%). Spearman’s correlation was 0.56 (p < 0.001). Sal-IgG and ser-IgG levels were correlated with age but not with gender, comorbidities, prolonged therapy, previous SARS-CoV-2 infection, or time from last COVID-19 infection/vaccination. The repeatability ranged from 23.8% (7.4 kAU/L) to 4.0% (3.77 kAU/L). The linearity of the assay was missed in 4/6 samples. No significant intrasubject differences were observed in sal-IgG across samples collected at different time points. Sal-IgG has good agreement with ser-IgG. Noninvasive saliva collection represents an alternative method for antibody measurement, especially in children.
唾液是一种前景广阔的基质,具有多种用途。我们的目的是验证唾液抗 SARS-CoV-2 抗体测定是否适用于监测免疫反应。帕多瓦大学医院共招募了 187 名受试者:其中女性 105 名(占 56.1%),男性 82 名(占 43.9%),儿童 95 名(占 50.8%),成人 92 名(占 49.2%)。受试者使用唾液采集器自行采集唾液;19 名受试者在一天内采集了三个不同的样本。所有受试者都采集了血清样本。N/S 抗 SARS-CoV-2 唾液 IgG(sal-IgG)和血清抗 SARS-CoV-2 S-RBD IgG(ser-IgG)用于测定抗 SARS-CoV-2 抗体。儿童的平均年龄(最小-最大)为 9.0 岁(1-18 岁),成人为 42.5 岁(20-61 岁)。在 187 份样本中,63 份(33.7%)sal-IgG 阴性,7 份(3.7%)ser-IgG 阴性。斯皮尔曼相关性为 0.56(p < 0.001)。Sal-IgG 和 ser-IgG 水平与年龄相关,但与性别、合并症、长期治疗、既往 SARS-CoV-2 感染或距上次 COVID-19 感染/接种疫苗的时间无关。重复性从 23.8%(7.4 kAU/L)到 4.0%(3.77 kAU/L)不等。4/6的样本未达到检测的线性度。在不同时间点采集的样本中,未观察到受试者内部 Sal-IgG 的明显差异。Sal-IgG 与 ser-IgG 具有良好的一致性。无创唾液采集是抗体测量的另一种方法,尤其适用于儿童。
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Antibodies
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