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Role of anti-inflammatory cytokine (IL10) in patients with chronic kidney disease.
Q3 Medicine Pub Date : 2025-02-12 DOI: 10.1177/10932607251317417
Duaa Mohammed Abdulsatar, Hayfaa Mahmood Fahad, Sahar Taha Hatif, Zaid Jaafar Awad Al-Nuaimi

Background: Anti-inflammatory cytokines is thought to influence the onset and course of chronic kidney disease (CKD). Particular cytokines include Interleukin-10 (IL-10), which is usually considered anti-inflammatory.

Objectives: The current study designed to determine the activity of the IL10 and their roles in chronic kidney disease.

Methods: This research is done, forty- five blood samples were collected from patients with chronic kidney disease and 42 volunteers. A sandwich ELISA was used to estimate the serum levels of human Interleukin-10.

Results: The mean age among patient groups (males, females) it was 47.40 ± 2.96 and 62.64 ± 14.46 years, respectively. While the control groups (males, females) were 40.97 ± 1.67 and 45.25 ± 7.13 years (p > 0.05). Of the 45 patients, 20 (44.4%) were males, 25 (55.6%) females. The resulted data showed that there are no significant (p > 0.05) for the total of the mean of human IL-10 between patients and control, respectively, where the mean level of IL10 in males was 190.10 ± 15.07& 154.18 ± 8.77 (p < 0.05) respectively and 142.22 ± 12.43 & 117.04 ± 14.66 in females, but not significantly (p > 0.05), and revealed an highly increased significant in this marker during the course of the chronic kidney disease in males more than females in patients (p < 0.05).

Conclusion: Can conclude from this study that decreased anti-inflammatory cytokine IL10 likely affects CKD progression and prognosis in females specifically.

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引用次数: 0
Amino acids characterization based on frequency and interaction analysis in human antigen-antibody complexes from Thera-SAbDab.
Q3 Medicine Pub Date : 2025-01-23 DOI: 10.1177/10932607241303614
Roylan Pais, Anil Kumar Nagraj, Akshata Gavade, Riya Patel, Mohasin Momin, Juergen Scheele, Werner Seiz, Jaspal Patil

Background: Antibodies are composed of light and heavy chains, both of which have constant and variable regions. The diversity, specific binding ability and therapeutic potential of antibodies are determined by hypervariable loops called complementarity-determining regions (CDRs), with the other regions being the framework regions.

Objective: To investigate the key amino acid patterns in various antibody regions in the human therapeutic antigen-antibody (Ag-Ab) complexes collected from the Thera-SAbDab database.

Method: The study focuses on identifying the amino acid frequency, diversity index in CDRs, paratope-epitope amino acid interactions, amino acid bond formation frequency, and bond types among selected therapeutic Ag-Ab complexes.

Results: The results revealed that Ser is highly distributed in the overall light chain CDRs while Gly is highly distributed in the heavy chain CDRs. CDR profiling analysis indicated that the average amino acid diversity in heavy chain CDRs is 60% to 70%, while in the light chain, it is 50% to 60%. Aromatic residues such as Tyr, Trp and Phe are the top contributors to these paratope-epitope interactions in the light and heavy chains. Moreover, we examined the frequency of amino acids in light and heavy chains of Ag-Ab complexes. Importantly, the outcome of this study leverages the in depth analysis on single residues, dipeptides, and tripeptides for the therapeutic Ag-Ab complexes.

Conclusion: We conclude that the amino acid frequency and interaction analysis centered on therapeutic Ag-Ab complexes will benefit antibody engineering parameters such as antibody design, optimization, affinity maturation, and overall antibody development.

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引用次数: 0
Emerging therapies in Multiple Myeloma: Leveraging immune checkpoint inhibitors for improved outcomes.
Q3 Medicine Pub Date : 2025-01-15 DOI: 10.1177/10932607241301699
Anuja Anil Mandavkar, Suraj Sai Nikhil Padakanti, Srajan Gupta, Samiyah Akram, Nida Jaffar, Jugalkishor Chauhan, Likhita Reddy Allu, Pulkit Saini, Jamil Nasrallah, Mohamed Abdullahi Omar, Muna Ali Mugibel, Saif Syed, Kumaran Ottilingam Ravindran, Ayush Dwivedi, Gurneet Singh Dhingra, Avleen Dhingra, Jay Kakadiya, Jana Kotaich, Shreya Singh Beniwal

Background:: Multiple Myeloma is a hematological malignancy characterized by the proliferation of clonal plasma cells and associated with severe clinical manifestations. Despite advancements in diagnosis and management, Multiple Myeloma remains incurable, necessitating further research into more effective therapies.

Aim:: The primary objective of this review is to provide an informative and critical summary of the Multiple Myeloma microenvironment, and emerging revolutionary therapeutic approaches with potential combination therapy to improve the quality of life for Multiple Myeloma patients.

Emerging approaches:: Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have shown improvements in immune response against Multiple Myeloma. ICIs target inhibitory pathways such as PD-1/PD-L1 and CTLA-4, potentially overcoming tumor-induced immunosuppression. Combination therapies integrate ICIs with proteasome inhibitors, immunomodulators, and monoclonal antibodies to enhance the anti-tumor immune response. Additionally, Chimeric Antigen Receptor T-cell (CAR-T) therapy has demonstrated effectiveness against Multiple Myeloma, particularly when coupled with ICIs to decrease resistance and relapse.

Challenges:: Although the efficacy of ICIs in treating Multiple Myeloma has been hindered by the complexity of the tumor microenvironment and immune evasion mechanisms, this challenge has led to the exploration of combination therapies. Potential side effects are still a big challenge for newly recognized ICIs and combination treatment.

Future directions:: Investigations of new immune checkpoints and the development of targeted therapies against these markers are in progress, creating possibilities for more personalized and effective treatment strategies. Continuous research and robust clinical trials are needed to comprehend the complex dynamics of the Multiple Myeloma microenvironment to develop revolutionary therapeutic targets.

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引用次数: 0
State of type 2 diabetic Iraqi patients after hospitalization for COVID-19.
Q3 Medicine Pub Date : 2025-01-15 DOI: 10.1177/10932607241304947
Hiba S Ahmed, Haylim N Abud, Hind S Ahmed

Background: The coronavirus-19 (COVID-19) pandemic, triggered by the severe acute respiratory syndrome coronavirus 2, has affected over 100 million people and killed around 2 million individuals. One of the most common chronic illnesses in the world is diabetes, which greatly raises the risk of hospitalization and death for COVID-19 patients.

Objective: This study aims to analyze the novel coronavirus's general characteristics and shed light on COVID-19 and its management in diabetic individuals by measuring some metabolic and inflammatory factors in type 2 diabetic patients with and without COVID-19.

Methods: One hundred Iraqi patients with type 2 diabetes mellitus (T2DM) were enrolled in the current study; 50 had COVID-19 with the Omicron variant, and 50 weren't. The diagnosis was designed by the consultant medical staff at the clinic. Eligible individuals had a positive nasal swab for reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 infection. They were compared with 50 healthy individuals as a control group. Every participant's anthropometric and clinical features were measured. The study includes the study groups' glycemic, lipid profile, serum urea, and C-reactive protein (CRP) measurements.

Results: There were remarkable rises (p < 0.05) in fasting and random blood glucose, serum lipid, and urea levels in diabetic patients with COVID-19 compared to those without COVID-19 and the control group. Also, a significant elevation (p = 0.01) was found in fasting serum insulin among diabetic patients with COVID-19 as compared to those without COVID-19 and the control group (32.75 ± 8.63 vs. 25.82 ± 3.50 and 10.65 ± 1.12) µU/L, respectively. Serum CRP levels significantly increased (p = 0.0001) in diabetic patients with COVID-19 compared to other groups.

Conclusion: Hyperglycemia, hyperinsulinemia, and dyslipidemia resulting from cytokine storm significantly increased the risk of hospitalization and death among coronavirus disease-19 patients. It has been concluded that T2DM reliably predicts morbidity among COVID-19 patients presenting with symptoms suggestive of severe hyperglycemia. The results also show the temporary and reversible deficiency in insulin secretion associated with severe acute respiratory syndrome coronavirus-2 infection. Consequently, it is recommended to examine variables of insulin sensitivity and pancreatic islet activity among patients with COVID-19 who have a history of diabetes.

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引用次数: 0
Assessment of CD40L and TSAB serum level in Graves disease patients. 评估巴塞杜氏病患者血清中的 CD40L 和 TSAB 水平。
Q3 Medicine Pub Date : 2024-09-23 DOI: 10.3233/HAB-240036
Alkhansaa Tariq Jawad, Hayfaa Mahmood Fahad, Ayat Ali Salih

Background: The autoimmune disorder known as Graves' disease. The condition is due to the binding of thyroid-stimulating immunoglobulins to the thyrotropin receptor located on the thyroid gland. The result is an excess of thyroidal hormones. symptoms of hyperthyroidism, and the formation of diffuse goiter.

Objectives: This research intends to quantify the levels of CD40L, TSAB in people who suffer from Graves' disease. It also aims to determine the relationship between TSAB and the duration of the disease, as well as analyze the role of CD40L as a predictive marker for Graves' disease using medcalc Statistical Software version 16.4.3 and SAS (2018).

Methods: In a case-control study, randomly selected 90 graves disease patients were included, the randomly selected patients were divided equally and matched into a case group who have graves disease and graves disease-free patients as a control group. For both groups whole blood sample was examined to compare for (TSAB), and (CD40L) levels determination by ELISA technique.

Results: The average serum levels of CD40L showed a highly significant correlation (P value < 0.01) among the groups examined for Graves' disease. The patient group consisted of 13 males (28.89%) and 32 females (71.11%). No significant correlation was identified between TSAB and the duration of the condition.

Conclusion: Thyroid stimulating antibody (TSAb) test and ultrasonography of the thyroid gland are valuable diagnostic techniques for autoimmune Graves' disease (GD). CD40L could potentially serve as a predictive diagnostic marker for Graves' disease. However, there is no observed link between the duration of the disease and the concentration of TSAB.

背景:巴塞杜氏病是一种自身免疫性疾病:巴塞杜氏病是一种自身免疫性疾病。这种疾病是由于刺激甲状腺的免疫球蛋白与位于甲状腺上的促甲状腺激素受体结合所致。其结果是甲状腺激素过多,出现甲状腺功能亢进症状,并形成弥漫性甲状腺肿:本研究旨在量化巴塞杜氏病患者体内的 CD40L 和 TSAB 水平。研究还旨在确定TSAB与病程之间的关系,并使用medcalc统计软件16.4.3版和SAS(2018)分析CD40L作为巴塞杜氏病预测标志物的作用:在病例对照研究中,随机选取90例巴塞杜氏病患者作为研究对象,将随机选取的患者平均分为病例组(患有巴塞杜氏病)和对照组(无巴塞杜氏病)。对两组患者的全血样本进行检测,通过酶联免疫吸附法测定(TSAB)和(CD40L)水平:结果:在接受检查的巴塞杜氏病患者组中,CD40L的平均血清水平显示出极显著的相关性(P值<0.01)。患者组中有 13 名男性(28.89%)和 32 名女性(71.11%)。TSAB与病程无明显相关性:结论:促甲状腺抗体(TSAb)检测和甲状腺超声波检查是自身免疫性巴塞杜氏病(GD)的重要诊断技术。CD40L有可能成为巴塞杜氏病的预测性诊断标志物。然而,在疾病的持续时间和TSAB的浓度之间并没有观察到任何联系。
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引用次数: 0
Development and characterization of three novel mouse monoclonal antibodies targeting spike protein S1 subunit of Middle East Respiratory Syndrome Corona Virus. 针对中东呼吸综合征冠状病毒尖峰蛋白 S1 亚基的三种新型小鼠单克隆抗体的开发和特征描述。
Q3 Medicine Pub Date : 2024-05-02 DOI: 10.3233/HAB-240016
A. Abbas, S. El-Kafrawy, Ashraf A Tabll, A. Hashem, Tagreed L Al Subhi, M. Alsaadi, E. Azhar
BACKGROUNDMiddle East Respiratory Syndrome Coronavirus is a highly pathogenic virus that poses a significant threat to public health.OBJECTIVEThe purpose of this study is to develop and characterize novel mouse monoclonal antibodies targeting the spike protein S1 subunit of the Middle East Respiratory Syndrome Corona Virus (MERS-CoV).METHODSIn this study, three mouse monoclonal antibodies (mAbs) against MERS-CoV were generated and characterized using hybridoma technology. The mAbs were evaluated for their reactivity and neutralization activity. The mAbs were generated through hybridoma technology by the fusion of myeloma cells and spleen cells from MERS-CoV-S1 immunized mice. The resulting hybridomas were screened for antibody production using enzyme-linked immunosorbent assays (ELISA).RESULTSELISA results demonstrated that all three mAbs exhibited strong reactivity against the MERS-CoV S1-antigen. Similarly, dot-ELISA revealed their ability to specifically recognize viral components, indicating their potential for diagnostic applications. Under non-denaturing conditions, Western blot showed the mAbs to have robust reactivity against a specific band at 116 KDa, corresponding to a putative MERS-CoV S1-antigen. However, no reactive bands were observed under denaturing conditions, suggesting that the antibodies recognize conformational epitopes. The neutralization assay showed no in vitro reactivity against MERS-CoV.CONCLUSIONThis study successfully generated three mouse monoclonal antibodies against MERS-CoV using hybridoma technology. The antibodies exhibited strong reactivity against MERS-CoV antigens using ELISA and dot ELISA assays. Taken together, these findings highlight the significance of these mAbs for potential use as valuable tools for MERS-CoV research and diagnosis (community and field-based surveillance and viral antigen detection).
背景中东呼吸综合征冠状病毒是一种高致病性病毒,对公共卫生构成重大威胁。目的本研究的目的是开发和鉴定针对中东呼吸综合征冠状病毒(MERS-CoV)尖峰蛋白 S1 亚基的新型小鼠单克隆抗体。对这些 mAbs 的反应性和中和活性进行了评估。这些 mAbs 是通过杂交瘤技术将骨髓瘤细胞和 MERS-CoV-S1 免疫小鼠的脾脏细胞融合产生的。结果表明,这三种 mAbs 对 MERS-CoV S1 抗原都有很强的反应性。同样,点式酶联免疫吸附试验(dot-ELISA)也显示了它们特异性识别病毒成分的能力,表明它们具有诊断应用的潜力。在非变性条件下,Western 印迹显示 mAbs 对 116 KDa 的特异性条带有很强的反应性,该条带与推测的 MERS-CoV S1 抗原相对应。然而,在变性条件下没有观察到反应带,这表明抗体能识别构象表位。结论 本研究利用杂交瘤技术成功制备了三种针对 MERS-CoV 的小鼠单克隆抗体。通过酶联免疫吸附和点酶联免疫吸附试验,这些抗体对 MERS-CoV 抗原有很强的反应性。综上所述,这些研究结果凸显了这些 mAbs 作为 MERS-CoV 研究和诊断(社区和现场监测以及病毒抗原检测)的重要潜在用途。
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引用次数: 0
The role of vitamin D against COVID-19 infection, progression and severity. 维生素 D 对 COVID-19 感染、进展和严重程度的作用。
Q3 Medicine Pub Date : 2024-04-10 DOI: 10.3233/HAB-240009
H. S. Ahmed, Hind Sh Ahmed, Haylim N. Abud
BACKGROUNDThe number of coronavirus disease-19 (COVID-19) positive patients and fatalities keeps rising. It is important to recognize risk factors for severe outcomes. Evidence linking vitamin D deficiency and the severity of COVID-19 is tangential but substantial - relating to race, obesity, and institutionalization.OBJECTIVEThis study aims to examine the function of vitamin D and nutritional defense against infections such as COVID-19, which is the goal of this research.METHODSThis study includes observational cohort, cross-sectional, and case-control studies that estimated variances in serum levels of vitamin D among patients with mild or severe forms of COVID-19, and in patients who died or were discharged from hospitals. Studies that assessed the risk of developing severe disorder or death in patients with vitamin D deficiency, defined as levels of vitamin D< 20 ng/mL, were also encompassed.RESULTSIn a retrospective study on 464,383 individuals, results showed that individuals who had the highest risks for severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, and for COVID-19 severity when infected, had vitamin D levels < 30 nmol/L; Odds Ratio (OR) were 1.246 [95% Confidence Interval (CI): 1.210-1.304] and 1.513 [95%CI: 1.230-1.861], respectively. Additionally, in a retrospective observational study of 191,779 individuals in the USA. The SARS-CoV-2 positivity rate was greater in the 39,190 subjects with vitamin D < 20 ng/mL [12.5%, 95% C.I. 12.2-12.8%] than in the 27,870 subjects with sufficient serum vitamin D levels [8.1%, 95% C.I. 7.8-8.4%] and in the 12,321 subjects with serum vitamin D ⩾ 55 ng/mL [5.9%, 95% C.I. 5.5-6.4%].CONCLUSIONPeople hospitalized for COVID-19 should be checked for vitamin D status and supplemented, and high-dose-in testing should be considered in the recovery trial. More importantly, screening for malnutrition and the administration of the best nutritional supplements are essential for the immune system of the human body to function as it should be. Thus, nutritional supplementation is crucial for people with risk factors as well as older adults with compromised immune systems.
背景冠状病毒病-19(COVID-19)阳性患者和死亡人数不断上升。认识导致严重后果的风险因素非常重要。本研究旨在探讨维生素 D 的功能和对 COVID-19 等感染的营养防御,这也是本研究的目标。方法本研究包括观察性队列研究、横断面研究和病例对照研究,这些研究估计了轻度或重度 COVID-19 患者以及死亡或出院患者血清中维生素 D 水平的差异。此外,还包括评估维生素 D 缺乏症(维生素 D 水平< 20 ng/mL)患者罹患严重疾病或死亡风险的研究。结果在一项对 464,383 人进行的回顾性研究中,结果显示感染严重急性呼吸系统综合征冠状病毒(SARS-CoV-2)和感染 COVID-19 严重程度风险最高的人的维生素 D 水平< 30 nmol/L;Odds Ratio (OR) 分别为 1.246 [95% Confidence Interval (CI):1.210-1.304] 和 1.513 [95%CI: 1.230-1.861]。此外,在一项针对美国 191 779 人的回顾性观察研究中。维生素 D < 20 ng/mL 的 39 190 名受试者的 SARS-CoV-2 阳性率[12.5%,95%C.I. 12.2-12.8%]高于血清维生素 D 水平充足的 27 870 名受试者[8.1%,95%C.I. 7.8-8.4%],也高于血清维生素 D 含量不足的 12 370 名受试者[8.1%,95%C.I. 7.8-8.4%]。结论COVID-19住院患者应检查维生素D状态并补充维生素D,在康复试验中应考虑高剂量检测。更重要的是,营养不良筛查和最佳营养补充剂的使用对于人体免疫系统发挥其应有功能至关重要。因此,对于有风险因素的人以及免疫系统受损的老年人来说,营养补充至关重要。
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引用次数: 0
The rebirth of epitope-based patent claims. 基于表位的专利申请的重生。
Q3 Medicine Pub Date : 2024-04-01 DOI: 10.3233/HAB-240006
Ulrich Storz
BACKGROUNDPatent protection of therapeutic antibodies and T cell receptors is an important tool to enable the path to the market. In view of the substantial spendings for R&D and regulatory approval, sponsors expect exclusivity for their drug for a given period of time. Different categories exist to protect therapeutic antibodies and T cell receptors. One of these categories are epitope-based patent claims, with regard to which in the different jurisdictions, different patentability standards exist, which, furthermore, are constantly changed by courts and lawmakers.OBJECTIVEThis article tries to explain the patentability issues related to epitope-based patent claims.METHODSFor this purpose, an overview is given on the respective legal provisions and court decisions.RESULTSThe study reveals that the respective patentability standards are constantly changed by courts and lawmakers.CONCLUSIONSCompanies developing therapeutic antibodies or T cell receptors need to consider these developments in their strategic planning.
背景治疗性抗体和 T 细胞受体的专利保护是帮助药物进入市场的重要工具。鉴于研发和监管审批花费巨大,申办者希望其药物在一定时期内享有独占权。治疗性抗体和 T 细胞受体有不同的保护类别。其中一类是基于表位的专利要求,不同的司法管辖区有不同的可专利性标准,而且法院和立法者也在不断修改这些标准。结论开发治疗性抗体或 T 细胞受体的公司需要在战略规划中考虑这些发展。
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引用次数: 0
Development and characterization of three novel mouse monoclonal antibodies targeting spike protein S1 subunit of Middle East respiratory syndrome corona virus. 针对中东呼吸综合征冠状病毒尖峰蛋白 S1 亚基的三种新型小鼠单克隆抗体的开发和特征描述。
Q3 Medicine Pub Date : 2024-01-01 DOI: 10.3233/HAB-240016
Aymn T Abbas, Sherif A El-Kafrawy, Ashraf A Tabll, Anwar M Hashem, Tagreed L Al Subhi, Mohammed Alsaadi, Esam I Azhar

Background: Middle East Respiratory Syndrome Coronavirus is a highly pathogenic virus that poses a significant threat to public health.

Objective: The purpose of this study is to develop and characterize novel mouse monoclonal antibodies targeting the spike protein S1 subunit of the Middle East Respiratory Syndrome Corona Virus (MERS-CoV).

Methods: In this study, three mouse monoclonal antibodies (mAbs) against MERS-CoV were generated and characterized using hybridoma technology. The mAbs were evaluated for their reactivity and neutralization activity. The mAbs were generated through hybridoma technology by the fusion of myeloma cells and spleen cells from MERS-CoV-S1 immunized mice. The resulting hybridomas were screened for antibody production using enzyme-linked immunosorbent assays (ELISA).

Results: ELISA results demonstrated that all three mAbs exhibited strong reactivity against the MERS-CoV S1-antigen. Similarly, dot-ELISA revealed their ability to specifically recognize viral components, indicating their potential for diagnostic applications. Under non-denaturing conditions, Western blot showed the mAbs to have robust reactivity against a specific band at 116 KDa, corresponding to a putative MERS-CoV S1-antigen. However, no reactive bands were observed under denaturing conditions, suggesting that the antibodies recognize conformational epitopes. The neutralization assay showed no in vitro reactivity against MERS-CoV.

Conclusion: This study successfully generated three mouse monoclonal antibodies against MERS-CoV using hybridoma technology. The antibodies exhibited strong reactivity against MERS-CoV antigens using ELISA and dot ELISA assays. Taken together, these findings highlight the significance of these mAbs for potential use as valuable tools for MERS-CoV research and diagnosis (community and field-based surveillance and viral antigen detection).

背景:中东呼吸综合征冠状病毒是一种高致病性病毒,对公共卫生构成严重威胁:中东呼吸综合征冠状病毒是一种高致病性病毒,对公共卫生构成重大威胁:本研究的目的是开发和鉴定针对中东呼吸综合征冠状病毒(MERS-CoV)尖峰蛋白S1亚基的新型小鼠单克隆抗体:在这项研究中,利用杂交瘤技术生成了三种针对 MERS-CoV 的小鼠单克隆抗体(mAbs),并对其进行了鉴定。对这些 mAbs 的反应性和中和活性进行了评估。这些 mAbs 是通过杂交瘤技术将骨髓瘤细胞和 MERS-CoV-S1 免疫小鼠的脾脏细胞融合产生的。利用酶联免疫吸附试验(ELISA)对杂交瘤产生的抗体进行筛选:结果:酶联免疫吸附试验结果表明,所有三种 mAbs 对 MERS-CoV S1 抗原都有很强的反应性。同样,点式酶联免疫吸附试验(dot-ELISA)也显示了它们特异性识别病毒成分的能力,表明它们具有诊断应用的潜力。在非变性条件下,Western 印迹显示 mAbs 对 116 KDa 的特异性条带有很强的反应性,该条带与推测的 MERS-CoV S1 抗原相对应。然而,在变性条件下没有观察到反应带,这表明抗体能识别构象表位。中和试验显示,抗体在体外对 MERS-CoV 没有反应:结论:本研究利用杂交瘤技术成功产生了三种抗 MERS-CoV 的小鼠单克隆抗体。结论:这项研究利用杂交瘤技术成功地产生了三种抗 MERS-CoV 的小鼠单克隆抗体,这些抗体在 ELISA 和点式 ELISA 检测中对 MERS-CoV 抗原有很强的反应性。综上所述,这些研究结果凸显了这些 mAbs 作为 MERS-CoV 研究和诊断(社区和现场监测以及病毒抗原检测)的重要潜在用途。
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引用次数: 0
Immunogenicity of biologics used in the treatment of asthma. 用于治疗哮喘的生物制剂的免疫原性。
Q3 Medicine Pub Date : 2024-01-01 DOI: 10.3233/HAB-240002
Omario A M Neunie, Wardah Rabbani, David Baker, Emma S Chambers, Paul E Pfeffer, Angray S Kang

Objective: Asthma is a major global disease affecting adults and children, which can lead to hospitalization and death due to breathing difficulties. Although targeted monoclonal antibody therapies have revolutionized treatment of severe asthma, some patients still fail to respond. Here we critically evaluate the literature on biologic therapy failure in asthma patients with particular reference to anti-drug antibody production, and subsequent loss of response, as the potential primary cause of drug failure in asthma patients.

Recent findings: Encouragingly, asthma in most cases responds to treatment, including the use of an increasing number of biologic drugs in moderate to severe disease. This includes monoclonal antibody inhibitors of immunoglobulin E and cytokines, including interleukin 4, 5, or 13 and thymic stromal lymphopoietin. These limit mast cell and eosinophil activity that cause the symptomatic small airways obstruction and exacerbations.

Summary: Despite humanization of the antibodies, it is evident that benralizumab; dupilumab; mepolizumab; omalizumab; reslizumab and tezepelumab all induce anti-drug antibodies to some extent. These can contribute to adverse events including infusion reactions, serum sickness, anaphylaxis and potentially disease activity due to loss of therapeutic function. Monitoring anti-drug antibodies (ADA) may allow prediction of future treatment-failure in some individuals allowing treatment cessation and switching therefore potentially limiting disease breakthrough.

综述的目的:哮喘是一种影响成人和儿童的全球性重大疾病,可因呼吸困难导致住院和死亡。尽管靶向单克隆抗体疗法已彻底改变了重症哮喘的治疗,但仍有一些患者无法对其产生反应。在此,我们对有关哮喘患者生物治疗失败的文献进行了批判性评估,特别提到了抗药物抗体的产生和随后的反应消失,这是导致哮喘患者药物治疗失败的潜在主要原因:令人鼓舞的是,哮喘在大多数情况下都能对治疗做出反应,包括在中重度疾病中使用越来越多的生物制剂药物。这包括免疫球蛋白 E 的单克隆抗体抑制剂和细胞因子,包括白细胞介素 4、5 或 13 和胸腺基质淋巴细胞生成素。小结:尽管抗体已经人源化,但苯拉利单抗、杜匹单抗、美博利珠单抗、奥马珠单抗、雷司利珠单抗和替塞单抗显然都会在一定程度上诱发抗药性抗体。这些抗体可能会导致不良事件,包括输液反应、血清病、过敏性休克以及因治疗功能丧失而导致的潜在疾病活动。监测抗药抗体(ADA)可预测某些患者未来的治疗失败,从而允许停止治疗和转换治疗方案,从而有可能限制疾病的突破。
{"title":"Immunogenicity of biologics used in the treatment of asthma.","authors":"Omario A M Neunie, Wardah Rabbani, David Baker, Emma S Chambers, Paul E Pfeffer, Angray S Kang","doi":"10.3233/HAB-240002","DOIUrl":"10.3233/HAB-240002","url":null,"abstract":"<p><strong>Objective: </strong>Asthma is a major global disease affecting adults and children, which can lead to hospitalization and death due to breathing difficulties. Although targeted monoclonal antibody therapies have revolutionized treatment of severe asthma, some patients still fail to respond. Here we critically evaluate the literature on biologic therapy failure in asthma patients with particular reference to anti-drug antibody production, and subsequent loss of response, as the potential primary cause of drug failure in asthma patients.</p><p><strong>Recent findings: </strong>Encouragingly, asthma in most cases responds to treatment, including the use of an increasing number of biologic drugs in moderate to severe disease. This includes monoclonal antibody inhibitors of immunoglobulin E and cytokines, including interleukin 4, 5, or 13 and thymic stromal lymphopoietin. These limit mast cell and eosinophil activity that cause the symptomatic small airways obstruction and exacerbations.</p><p><strong>Summary: </strong>Despite humanization of the antibodies, it is evident that benralizumab; dupilumab; mepolizumab; omalizumab; reslizumab and tezepelumab all induce anti-drug antibodies to some extent. These can contribute to adverse events including infusion reactions, serum sickness, anaphylaxis and potentially disease activity due to loss of therapeutic function. Monitoring anti-drug antibodies (ADA) may allow prediction of future treatment-failure in some individuals allowing treatment cessation and switching therefore potentially limiting disease breakthrough.</p>","PeriodicalId":53564,"journal":{"name":"Human Antibodies","volume":" ","pages":"121-128"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Human Antibodies
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