Human Antibodies - Volume Pre-press, issue Pre-press

Authors: Kolivand, Sedighe | Nazari, Mahboobeh | Modarressi, Mohammad Hossein | Najafabadi, Mohammad Reza Hosseini | Hemati, Atefeh | Ghafouri-Fard, Soudeh | Motevaseli, Elahe

Article Type: Research Article

Abstract: BACKGROUND: Inhibin A, a member of TGF-β superfamily, consists of α and β subunits. These subunits contain several cysteine residues in amino acid sequence that forms inter- and intra-subunits disulfide bonds. Due to the reducing environment of the bacterial cytoplasm, disulfide bonds formation in E.coli cytoplasm is not possible. Therefore, this can cause misfolding, aggregation and inclusion bodies formation during protein expression. As a result, the expression of inhibin subunits in E.coli produces inclusion bodies OBJECTIVE: We aimed at identification of an optimized protocol for …expression and recovery of inhibin α -subunit from inclusion bodies. METHOODS: Two vectors, four different E.coli strains, and six solubilization conditions for were used for the optimization of inhibin α -subunit production. Then, the solubilized proteins were purified through Ni-NTA affinity chromatography, characterized by SDS-PAGE and Western blotting (WB) using anti-his tag antibody, and refolded by dilution. RESULTS: The results showed that inhibin α -subunits were successfully expressed in both vectors and the pET22b+ inhibin α -subunit in Shuffle TM T7 strain had the highest expression; however, most of the expression was in an insoluble form. Among solubilization buffers examined, a buffer containing 2M urea with pH 12 was the best buffer to dissolve the insoluble protein. The high purity of protein was confirmed by SDS-PAGE and WB. Non-reducing SDS-PAGE demonstrating inhibin α -subunit refolded well. Show more

DOI: 10.3233/HAB-190399

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Fallah, Hamid | Akbari, Mohammad Taghi | Mirzajani, Sara | Ranjbaran, Fatemeh | Mehdizadeh, Bijan | Sayad, Arezou | Taheri, Mohammad

Article Type: Research Article

Abstract: Celiac disease (CD) is a common autoimmune disease that is manifested by inflammation of the small intestine and varying extra intestinal symptoms, also considered to be associated with human HLA-DQ genes. In this study, 40 patients of CD and 40 healthy control samples were genotyped for HLA-DQB1 and 14 patients of CD and 14 healthy control samples were genotyped for HLA-DQA1genes using the SSP-PCR technique and a commercial kit. The DQA1*05 allele had the highest frequency among the patient group (42.86%). The frequency of this allele was 28.57% in healthy controls, and there was no statistically significant difference in …this case (p = 0.771). The DQB1*02 allele was the most common in patients (33.75%) followed by the DQB1*03 allele (31.25%). The difference in frequency of the HLA-DQB1*02 allele in the patient and control groups was statistically significant (P = 0.0002, OR = 4.72). The remarkable differences in the distribution of HLA-DQ2 in Iranian patients compared to controls and relative risks signified the role of these alleles in the development of CD in Iranian patients and confirmed the likelihood of using HLA-DQ typing in the substantiation of the disease. Show more

Keywords: Celiac disease, HLA, immune response

DOI: 10.3233/HAB-190398

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Barabas, Arpad Z. | Cole, Chad D. | Kovacs, Zoltan B. | Kovacs, Erno I. | Lafreniere, Rene | Weir, Donald Mackay

Article Type: Research Article

Abstract: In spite of enormous efforts there have been no solutions to date for preventing/terminating certain acute and chronic disorders of humans by vaccination or drugs. Yet it is well understood that if the target antigen (ag) could be presented appropriately to the cells of the immune system then solutions could be found. Recently, the Barabas research group has introduced and described the third vaccination method – called modified vaccination technique (MVT) – which has the ability to provide a corrective immune response in experimental animals with an autoimmune kidney disease. Injections of immune complexes – made up of the target …ag and specific non-pathogenic IgM antibodies directed against the target ag – achieved downregulation of pathogenic immune responses and tolerance to self was regained. Utilizing the immune system’s natural abilities to respond to corrective information, the MVT technique was able to prevent an autoimmune kidney disease from occurring (prophylactic effect) in experimental animals, and when present, terminating it (therapeutic effect) specifically and without measurable side effects. It is predicted that the application of the MVT will have the potential in the future to revolutionize the preventative and therapeutic options for dealing with chronic disorders in humans (such as autoimmune disease, cancer and acute chronic infections) and achieve cures. Show more

Keywords: Autoimmune disease, modified vaccination technique, slowly progressive Heymann nephritis, membranous glomerulonephritis, autoantibody

DOI: 10.3233/HAB-190396

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Alidoost, Saeideh | Habibi, Mohsen | Noormohammadi, Zahra | Hosseini, Jalil | Azargashb, Eznollah | Pouresmaeili, Farkhondeh

Article Type: Research Article

Abstract: BACKGROUND: Prostate cancer (PCa) as the first men’s common cancer in the world and the third cancer in Iranian men is a heterogeneous disorder which sometimes several biopsies are needed for its diagnosis. OBJECTIVES: The aim of current study is finding new biomarkers in order to diagnose of PCa at the earliest possible stage. Hence, the relationship between rs1800629 and rs361525 polymorphisms of TNF-α gene with PCa was investigated. MATERIALS AND METHODS: Blood DNA samples were collected from 100 patients with PCa, 110 with BPH, and 110 controls. Collected …samples were examined using PCR-RFLP and Tetra-ARMS-PCR techniques to detect the desired polymorphisms. RESULTS: The frequency of rs1800629 genotypes in smokers was significantly different from non-smokers with PCa (p = 0.001). Logistic regression analysis results showed that GA heterozygotes in comparison to GG homozygotes had higher risk of developing Benign Prostatic Hyperplasia (BPH) or prostate cancer. However, no significant correlation was considered between the risk of PCa and the TNF-α gene polymorphisms (rs1800629 and rs361525). CONCLUSIONS: Although, the achieved results of this investigation demonstrated that the two examined genetic variants do not seem to be suitable markers for early diagnosis of prostate cancer in this pilot study; however increased risk for the disease is shown in GA heterozygotes and smokers which is indicative of some epigenetic factors influence on prostate cancer etiology. Show more

Keywords: Prostate cancer, benign prostate hyperplasia, TNF-α polymorphism

DOI: 10.3233/HAB-190397

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Alemayehu, Yisak Hagos | Seylani, Khatereh | Bahramnezhad, Fatemeh

Article Type: Research Article

Abstract: BACKGROUND: Various studies have highlighted the correlates to health literacy and quality of life among patients receiving hemodialysis therapy. However, evidence of how these two outcomes could influence each other is not clear. OBJECTIVE: This study aimed to assess the correlation between health literacy and quality of life among patients receiving hemodialysis. METHODS: This is an integrative review of correlational studies. This study conforms to the preferred reporting items for integrative reviews described by Whitemore and Knafl. We search for studies reporting on the correlation of health literacy and quality of life among …patients receiving hemodialysis in six databases, that is PubMed, Web of Science/Knowledge, Scopus and Embase, Google Scholar and Ovid MEDLINE. RESULTS: In this review five studies were included after screening them against the inclusion criteria. Two studies were identified from Iran, and one study was identified each from Australia, Turkey, and the USA. Most studies were descriptive comparative in nature, while two studies were experimental. Shayan’s study had the highest number of participants. This study reports on 1,063 patients receiving dialysis. Most studies were conducted at different centers. Findings from three studies showed that there was a significant relationship between health literacy and quality of life among patients receiving hemodialysis. CONCLUSION: There is a relationship between health literacy and quality of life among patients receiving hemodialysis. Conclusively, addressing health literacy may improve the quality of life among patients receiving hemodialysis. Show more

Keywords: Health literacy, quality of life, hemodialysis, integrative review, health-related quality of life, renal dialysis, kidney disease, End Stage Renal Disease

DOI: 10.3233/HAB-190394

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Storz, Ulrich

Article Type: Research Article

Abstract: Epitope-based antibody claims have emerged to become one of the most important claim species in antibody patents. At the same time, they are heavily disputed. This article strives to give an overview about the as is situation both in Europe and the United States.

Keywords: Patent, antibody, epitope, target, competition

DOI: 10.3233/HAB-190395

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-22, 2019

Authors: Fatehi, Razieh

Article Type: Research Article

Abstract: Two classes of T helper lymphocytes, Th1 and Th2 have different roles in B cell activation based on specific cytokines. To understand molecular mechanisms of B cell activation, the microarray dataset of B cells co-cultured with type 1 and 2 T helper, Be1 and Be2, were investigated. After quality assessment, using the GEO2R tool, the GSE84948 dataset was re-analyzed. Genes with adjusted p -value ⩽ 0.05 were assumed as differentially expressed (DE). The protein-protein interaction (PPI) networks were constructed using CluePedia plugin of Cytoscape, and analyzed by NetworkAnalyzer tool and MCODE plugin. Using ClueGO plugin …of Cytoscape software, gene ontology (GO) analysis was performed. The comparison of Be1 and Be2 cells with naive B cells revealed 8742 and 8748 DE genes, respectively. The topology analysis of PPI networks predicted central genes. Among these, Jak3, Actrt3, and Pik3cb genes were determined as crucial genes in Be1 network. Prkx, Smarca4, and Jak2 genes were defined crucial gene in Be2 PPI network. GO analysis with PPI networks genes resulted which most of the terms are related to immune system activation. In conclusion, we explored holistic methods for molecular assay of difference between B cell activation mechanisms with Th1 and Th2. Show more

Keywords: T-Lymphocytes, helper-Inducer, cytokines, microarray, protein interaction network, gene ontology

DOI: 10.3233/HAB-190393

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-5, 2019

Authors: Khazaei, Mojtaba | Davoodian, Arezou | Taheri, Mohammad | Ghaforui-Fard, Soudeh

Article Type: Research Article

Abstract: BACKGROUND: One of the concerns in patients with acute ischemic stroke with former history of taking antiplatelet drugs is the risk of intracerebral hemorrhage following venous thrombolysis. The purpose of this study was to evaluate the effect of previous administration of antiplatelet drugs on adverse outcomes of recombinant tissue plasminogen activator (tPA) in patients with acute ischemic stroke. METHODS: In this study, 46 patients with the diagnosis of acute ischemic stroke were recruited. Patients were assessed in a period of three hours after stroke and received the standard dose of tPA (0.9 mg/kg). History of antiplatelet …drugs, risk factors, demographic information and stroke severity were collected. The severity of the stroke was determined by the National Institutes of Health Stroke Scale (NIHSS). The outcome was assessed using the Modified Rankin Scale (MRS) and Barthel Index (BI) in the days one, 14 and 90. RESULTS: Patients with history of antiplatelet drugs had an increased rate of intracranial hemorrhage [odds ratio (95% CI) = 7.3 (1.3–40.5)]. Stroke severity scores were higher in patients receiving antiplatelet drugs than the other group at discharge day and day 90. In both groups, the severity of the disease decreased with time. Mortality rate was 42.1% in patients received antiplatelet drugs and 18.5% in the other group (P > 0.05). CONCLUSION: Based on the results of this study, patients with acute ischemic stroke and history of taking antiplatelet drugs have poor outcome following administration of standard dose of tPA. Show more

Keywords: tPA, antiplatelet drug, intracerebral hemorrhage

DOI: 10.3233/HAB-190391

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-4, 2019

Authors: Dashti, Sepideh | Taherian-Esfahani, Zahra

Article Type: Research Article

Abstract: BACKGROUND: Cancer-germline genes are a class of genes that are normally expressed in testis, trophoblast and few somatic tissues but abnormally expressed in tumor tissues. Their expression signature indicates that they can induce cellular immune responses, thus being applied as targets in cancer immunotherapy. OBJECTIVES: To obtain the data of cellular immune responses against cancer-germline genes in cancer. METHODS: We searched PubMed/Medline with the key words cancer-germline antigen, cancer-testis antigen, CD4+ T cell, CD8+ T cell and cancer. RESULTS: About 40 cancer-germline genes have …been shown to induce T cell specific responses in cancer patients. Melanoma, lung and breast cancer are among the mostly assessed cancer types. Several epitopes have been identified which can be used in immunotherapy of cancer. CONCLUSION: Cellular immune responses against cancer-germline genes are indicative of appropriateness of these genes as therapeutic targets. Show more

Keywords: Cancer-germline gene, cancer-testis antigen, immune response, T cell, cancer

DOI: 10.3233/HAB-190392

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Mir, Manzoor A. | Mehraj, Umar | Sheikh, Bashir Ahmad | Hamdani, Syed Suhail

Article Type: Research Article

Abstract: Antibodies represent a well-established class of clinical diagnostics for medical applications as well as essential research and biotechnological tools. Although both polyclonal and monoclonal antibodies are indispensable reagents in basic research and diagnostics but both of them have their limitations. Hence, there is urgent need to develop strategies aimed at production of alternative scaffolds and recombinant antibodies of smaller dimensions that could be easily produced, selected and manipulated. Unlike conventional antibodies, members of Camelidae and sharks produce antibodies composed only of heavy chains with small size, high solubility, thermal stability, refolding capacity and good tissue penetration in vivo . The …discovery of these naturally occurring antibodies having only heavy-chain in Camelidae family and their further development into small recombinant nanobodies represents an attractive alternative in drug delivery, diagnostics and imaging. Nanobody derivatives are soluble, stable, versatile, have unique refolding capacities, reduced aggregation tendencies and high-target binding capabilities. They can be genetically customized to target enzymes, transmembrane proteins or molecular interactions. Their ability to recognize recessed antigenic sites has been attributed to their smaller size and the ability of the extended CDR3 loop to quickly penetrate into such epitopes. With the advent of molecular engineering and phage display technology, they can be of potential use in molecular imaging, drug delivery and therapeutics for several major diseases. In this review we present the recent advances in nanobodies for modulating immune functions, for targeting cancers, viruses, toxins and microbes as well as their utility as diagnostic and biosensor tools. Show more

Keywords: Recombinant antibodies, nanobody, drug delivery, cancer, diagnostics, chimeric, humanized antibodies, immunoaffinity chromatography, site directed mutagenesis

DOI: 10.3233/HAB-190390

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-23, 2019