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

Authors: Mayrhofer, Patrick | Kunert, Renate

Article Type: Research Article

Abstract: Nomenclature of monoclonal antibodies traditionally followed a strict scheme indicating target and species information. Because of the rapid advances in this field, emphasized by approval of four humanized and six human antibodies in 2017, the International Nonproprietary Name of new antibodies was updated profoundly by removing the species substem completely. In this review we give an overview about what developments led to the preference of the scientific community towards human-like antibodies. We summarize the major updates in naming schemes that tried to classify antibodies according to their humanization technique or to the final primary sequence and how this led to …the erroneous perception to indicate expected immunogenicity. Following the new 2017 nomenclature update, there will not be any information available about the species origin in the names of new antibodies, which emphasizes the need for providing additional supplemental information to the scientific community and develop tools to accurately estimate and control the safety of new monoclonal antibody molecules. Show more

Keywords: USAN, antibody immunogenicity, CDR grafting, superhumanization

DOI: 10.3233/HAB-180347

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-15, 2018

Authors: Eftekharian, Mohammad Mahdi | Omrani, Mir Davood | Arsang-Jang, Shahram | Taheri, Mohammad | Ghafouri-Fard, Soudeh

Article Type: Research Article

Abstract: Schizophrenia is a chronic severe mental disorder in which immunologic imbalances have been reported. Some researchers have demonstrated dysregulation of cytokine levels in this mental disorder. Considering the possible role of cytokines in the pathogenesis or clinical course of schizophrenia, we assessed serum levels of IL-4, IL-10, IL-17A and IFN-γ in a homogenous sample of Iranian patients who were in remission under treatment with Clozapine compared with sex and age matched controls. There was a statistically significant difference in IL-4 levels between patients and healthy subjects (P = 0.023). IL-4 levels were …83% higher in cases than in control group. No significant group*gender interaction was detected suggesting the similar IL-4 levels between males and females in each study group. There was no statistically significant difference in IFN-γ levels between patients and healthy subjects, but IFN-γ levels were 70% higher in male compared with female group. No significant differences have been found in serum levels of other cytokines between cases and controls or between males and females. The higher levels of IL-4 in patients treated with Clozapine might be due to effects of this antipsychotic drug on immune responses. Future studies are needed to elaborate the exact underlying mechanism. Show more

Keywords: Schizophrenia, IL-4, IL-10, IL-17A, IFN-γ

DOI: 10.3233/HAB-180344

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Zarei, Adi Essam | Redwan, Elrashdy M.

Article Type: Research Article

Abstract: Our previous results showed higher level of anti-Hib IgG (2.41 μ g/ml) average geometric mean concentration (GMC) regardless of age and gender, followed by levels of IgM (0.91 μ g/ml) and IgA (0.34 μ g/ml), reflecting the prevalence of immunity against Hib. Current study was evaluated the avidity profile for these high anti-Hib concentration. The IgM avidity analysis did not revealed any significant results between male and female values. While, the average of IgA avidity in male samples were significantly (P < 0.05) higher than the average of female. Also, The result …showed that high percentage of population has moderate to high IgG avidity. The study showed lower avidity percentages of both IgM and IgA comparing to IgG. More studies are suggested to be done on individuals with low avidity considering the secondary immunodeficiency in participant’s history. Show more

Keywords: Haemophilus influenzae type b (Hib), anti-polyribosyl-ribitol phosphate (PRP), conjugate vaccine, prevalence, antibodies avidity

DOI: 10.3233/HAB-180345

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Sardarian, Khosro | Maghsood, Amir Hossein | Farimani, Marzieh | Hajiloii, Mehrdad | Saidijam, Masoud | Farahpour, Manizheh | Mahaki, Hanie | Zamani, Alireza

Article Type: Research Article

Abstract: BACKGROUND: Congenital toxoplasmosis is an important disease that occurs when pregnant women become infected with Toxoplasma gondii during pregnancy. The aim of this study was to investigate the presence of T. gondii B1 gene in placental tissues of IgM seronegative women. MATERIALS AND METHODS: In this research, chronic toxoplasmosis was identified through examination of blood samples in a group of pregnant women by anti-Toxoplasma IgG and IgM ELISA and nested-PCR techniques. IgG avidity test was used to estimate the onset of infection in some pregnant women with chronic infection. After delivery, some umbilical …cord and neonatal blood were tested by anti-Toxoplasma IgM ELISA, and also the B1 gene of T. gondii was investigated in their placental tissue by nested-PCR. Some factors such as blood sampling time and some clinical symptoms experienced during pregnancy were recorded. RESULTS: One hundred and sixty seven out of 653 (25.6%) pregnant women were positive for anti-Toxoplasma IgG. Of them, 165 (98.8%) were negative for anti-T. gondii IgM. Six out of 10 (60%) placental tissues from IgG seropositive, IgM seronegative women were positive for T. gondii B1 gene, while anti-Toxoplasma IgM was negative in the umbilical cord and neonatal blood samples. The results of IgG avidity test showed low avidity in one and high avidity in two women’s samples. The B1 gene was not found in the blood samples of any of the six mothers. The most symptoms experienced during pregnancy were headache and nausea. CONCLUSION: The detection of B1 gene in placental tissues of the healthy newborn infants reiterates that presence of T. gondii in the placenta does not always result in congenital toxoplasmosis. Show more

Keywords: Congenital toxoplasmosis, placenta, polymerase chain reaction

DOI: 10.3233/HAB-180346

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-5, 2018

Authors: Zarei, Adi Essam | Redwan, Elrashdy M.

Article Type: Research Article

Abstract: Our previous reported that Jeddah, Saudi Arabia population have a comparable and protective herd immunity represented by IgG, IgA and IgM against Haemophilus influenzae type b (Hib), by using indirect ELISA test was used to evaluate Haemophilus influenzae type b (Hib) anti-polyribosyl-ribitol phosphate (PRP) total antibodies (IgM, IgG, IgA) in 1,003 sera samples. Current report was evaluated the IgG and IgA subclasses responsible about this protection using same methodology. IgG, IgA, and their subclasses are responsible about this circulating protection. Our study will consider the first report evaluate the levels of IgA subclasses and its relation to ages, as …well as the relations between anti-Hib antibody subclass and age. The current results demonstrated that the highest levels concentrated in IgG1 and IgG2, while IgG3 and IgG4 showed the lowest levels. So, their concentrations were arranged in IgG1 > IgG2 > IgG3 > IgG4. The results indicated that the age and gender have no effect on both IgG or IgA subclasses in healthy immunized individuals enrolled. While, IgA1 concentrations were significantly higher than IgA2 in all age categories regardless of gender. It seem that the IgG1, IgG2 and IgA1 subclasses were the main constituent of Jeddah herd immunity against Hib. Finally, to the best of our knowledge, there were no previous reports that focusing on the levels of IgA subclasses and its relation to ages, so our study considers the first worldwide. Show more

Keywords: Haemophilus influenzae type b (Hib), anti-polyribosyl-ribitol phosphate (PRP), conjugate vaccine, antibodies, Subclasses, IgG1, IgG2, IgG3, IgG4, IgA1, IgA2

DOI: 10.3233/HAB-180343

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Zarei, Adi Essam | Redwan, Elrashdy M.

Article Type: Research Article

Abstract: In this national comprehensive seroprevalence study, indirect ELISA test was used to evaluate Haemophilus influenzae type b (Hib) anti-polyribosyl-ribitol phosphate (PRP) total antibodies (IgM, IgG, IgA) in 1,003 sera samples from routine medical check-up of healthy individuals attending the local medical facility in Jeddah, Saudi Arabia in the period from February 2014 to January 2016. Serum anti-CPS antibodies confer immunity against invasive Hib disease. An anti-CPS concentration of ⩾  0.15 μ g/mL is believed to be a serological indication for short-term immunity protection against invasive Hib disease, while a concentration of ⩾ …1.0 μ g/mL is believed to be long-term protective. Results showed higher level of anti-Hib IgG (2.41 μ g/ml average geometric mean concentration (GMC) regardless of age and gender, followed by levels of IgM (0.91 μ g/ml) and IgA (0.34 μ g/ml), reflecting the community immunity against Hib. Low anti-Hib level (< 0.15 μ g/ml of anti-PRP IgG) in elderly people (males aged 57–91 years and females aged 35–64 years) may indicate a need for a booster dose of Hib vaccine to elderly people in the community. The IgG prevalence over IgM, and IgM prevalence over IgA indicate the major role of IgG over IgM and IgA in keeping immunity in the track against Hib. Low level of IgM and IgA comparing to IgG may indicate the absence of Hib acute infections in the population. Show more

Keywords: Haemophilus influenzae type b (Hib), anti-polyribosyl-ribitol phosphate (PRP), conjugate vaccine, prevalence, antibodies

DOI: 10.3233/HAB-180342

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Sayad, Arezou | Salmani, Tayyebali | Hemmesi, Maryam Kazemzadeh | Ganji, Maziar | Ghafouri-Fard, Soudeh | Hatami, Mahsa | Soudyab, Mohammad | Taheri, Mohammad

Article Type: Research Article

Abstract: Multiple sclerosis (MS) is an autoimmune disease characterized by recurrent episodes of demyelination and loss of oligodendrocytes. The demyelination process is caused by various subsets of CD4+ T cells with a Th1 and Th17 phenotype. The retinoid acid-related orphan receptor A (RORA ) is expressed in Th17 cells and promote Th17 differentiation. In this study, we compared the expression level of RORA gene in the blood of 50 relapsing-remitting MS (RRMS) patients who were treated with IFN-β and 50 healthy controls by TaqMan Quantitative Real-Time PCR. We found that RORA expression …was significantly down-regulated in MS patients compared with controls (P = 0.006). However, there was no significant correlation between RORA gene expression and Kurtzke Expanded Disability Status Scale (EDSS). Our findings suggest a possible contribution of IFN-β in the downregulation of RORA . In addition, RORA downregulation may be a potential indicator of positive response to interferon beta treatment of multiple sclerosis patients. Show more

Keywords: Multiple sclerosis, RORA, IFN-β

DOI: 10.3233/HAB-180341

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-6, 2018

Authors: Atefeh, Hemati | Mahnaz, Azarnia | Mohammadhosein, Modaresi | Amir, Rahimi

Article Type: Research Article

Abstract: BACKGROUND: Generation and utilization of the specific monoclonal antibodies against testis antigens is reported to identify the antigens that are important in reproductive field. OBJECTIVE: Current study aimed to introduce a hybridoma that producing a specific anti-testis monoclonal antibody to identify the testis antigens that can be important in the reproduction field. METHODS: To make hybridoma against testis antigens, mice were immunized with testis cell lysate. After cell fusion, resulted hybridomas were screened by indirect ELISA, then cloned by limiting dilution and finally the produced monoclonal antibody were characterized by some of the molecular …laboratory techniques such as immunohistochemistry, immunocytochemistry and western blot. RESULTS: By using hybridoma technique, cell fusion was performed and ten (8A11, 8D6, 8D7, 9F6, 9G11, 10C3, 10B3, 10B2, 10C2 and 10H7) antibodies specific to the testis antigens were produced finally. Among the produced antibodies, 10C3 was found to cross-react with testis, but not detected in other tissues. mAb 10C3 recognized the sperm and testis antigens, specifically the intertestitial tissue of testis, spermatogonia, primary and secondary spermatocyte antigens, so they were most likely the target of generated mAb. Also our mAb could totally detect the mouse sperm antigens and the specific antigens of head and tail of human sperm. In western blotting analysis, mAb 10C3 could recognize the specific protein bands of sperm and testis extracts. Also in this study the testis specific genes that were target of generated mAb, were selected according to the mouse EST profile available at UniGene part of NCBI. CONCLUSIONS: So this stable anti-testis mAb has a potential for laboratory researches and also for diagnostic procedures in fertilization. Thus it could be exploited as a suitable tool for target-specific diagnosis and research in several diseases. Show more

Keywords: Hybridoma, monoclonal antibodies, spermatogenesis, testis, fertilization

DOI: 10.3233/HAB-180340

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Willis, R. | Smikle, M. | Heslop, O. | Bodonaik, N. | Thame, M. | Kumar, U. | Aung, M. | Kellier, A. | Drysdale, S. | Leon, V.

Article Type: Research Article

Abstract: BACKGROUND: Pneumococcal serotypes circulating in any population vary over time and between countries and impacts the effectiveness of pneumococcal vaccination. OBJECTIVE: This study investigated the epidemiology of pneumococcal disease in Jamaica. METHODS: Streptococcus pneumoniae isolates (n = 349) along with demographic and clinical information were collected from patients presenting at the 4 major hospitals in Jamaica over a 2-year period. Serotyping was done using latex agglutination tests and the Quellung reaction assay. RESULTS: Invasive pneumococcal disease (IPD) incidence was 45.4/100,000 in children under 5 yrs and 16.3/100,000 …in adults over 65 yrs. Thirteen serogroups were identified among the 120 isolates subjected to grouping; the most common being serogroups: 19 (22/120,18.3%), 6 (20/120,16.7%), 14 (20/120,16.7%), 23 (18/120,15.0%), 3 (11/120,9.2%) and nontypeable (8/120,2.3%). The estimated vaccine coverage rates for the PCV7 and PCV13 vaccines in children less than 5 yrs were 82.5% and 88.7% respectively. The 23-valent PPV23 provided 100% coverage rate in adults over 65 yrs and 82.9% coverage rate for the entire population. CONCLUSIONS: Pneumococcal vaccine coverage rates in Jamaica are comparable to those reported in certain developed countries and higher than in other developing countries. The high incidence of IPD in the paediatric population indicates that routine vaccination would be beneficial. Show more

Keywords: Streptococcus pneumoniae, pneumococcus, vaccine, serotype, Serogroup, Jamaica, Epidemiology

DOI: 10.3233/HAB-180338

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Moravvej, Hamideh | Tabatabaei-Panah, Pardis-Sadat | Ebrahimi, Elaheh | Esmaeili, Nafiseh | Ghaderian, Sayyed Mohammad Hossein | Ludwig, Ralf J. | Akbarzadeh, Reza

Article Type: Research Article

Abstract: BACKGROUND: TNF-α -308G/A polymorphism has been investigated in few studies for an association with susceptibility to bullous pemphigoid (BP) and alopecia areata (AA). Yet, these findings had so far not been independently replicated, and no data on a possible association of TNFα -308G/A polymorphism with these diseases in Iranian population were available. OBJECTIVES: In the present study, a possible effect of TNF-α -308G/A variation on susceptibility to BP or AA disease was evaluated. METHODS: Genomic DNA was extracted from the blood of the patients …with BP and AA as well as control subjects which genotyped for the TNF-α -308 G/A polymorphism. TNF-α gene expression levels were analyzed by real-time RT-PCR. RESULTS: No association was observed between the TNF-α -308 G/A variation and susceptibility to BP or AA diseases in our Iranian cohort. In contrast to AA patients, expression of TNF-α gene was significantly higher in BP patients compared to control group. TNF-α gene was found to be similarly expressed in mutant and wild-type genotypes. CONCLUSIONS: TNF-α -308G/A polymorphism is not associated with the risk to develop of BP and AA in our Iranian cohort. Furthermore, this polymorphism is not contributed to altering the levels of gene expression in both diseases. Show more

Keywords: Tumor necrosis factor-α, polymorphism, gene expression, bullous pemphigoid, alopecia areata

DOI: 10.3233/HAB-180339

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-7, 2018