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

Authors: Manoochehrabadi, Saba | Arsang-Jang, Shahram | Mazdeh, Mehrdokht | Inoko, Hidetoshi | Sayad, Arezou | Taheri, Mohammad

Article Type: Research Article

Abstract: BACKGROUND: Multiple sclerosis (MS) is the most common chronic, inflammatory, autoimmune disease of the central nervous system (CNS) maintained by the secretion of a large number of cytokines [1]. The signal transducer and activator of transcription (STAT ) family has an essential role in transmitting many of the cytokine-mediated signals and failure in the signaling process contributes to the etiopathogenesis of MS. METHODS: This study aimed to assess STAT1 , STAT2 and STAT3 gene expression in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls by TaqMan Quantitative Real-Time PCR. …RESULTS: The results showed that STAT1 gene expression was significantly up-regulated (p = 0.023), whereas STAT2 gene expression was significantly down-regulated (p < 0.0001) in MS patients compared to controls. On the other hand, there was no significant difference between MS patients and controls for STAT3 gene expression (p = 0.837). In addition, there was no significant correlation between the expression of STAT1 , STAT2 , STAT3 genes and clinical findings, such as the level of physical disability in MS patients (according to the Kurtzke Expanded Disability Status Scale (EDSS) criterion) and disease duration. CONCLUSION: A significant positive correlation was demonstrated between STAT1 and STAT2 and also between STAT1 and STAT3 . This study shows for the first time that a comparison of the relative quantitative expression of three different STAT genes in the blood cells of MS patients compared to controls revealed marked differences in the expression of the STAT family genes that might reflect their different roles in the pathogenesis of MS. These transcripts might be useful biomarkers for evaluating the efficacy of IFN treatment of the MS patients. Show more

Keywords: Multiple sclerosis, STAT1, STAT2, STAT3

DOI: 10.3233/HAB-180352

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-8, 2018

Authors: Almehdar, Hussein A. | El-Baky, Nawal Abd | Alhaider, Abdulqader A. | Redwan, Elrashdy M.

Article Type: Research Article

Abstract: Secretory lactoferrins play a crucial rolls at mucosal surfaces as not only antimicrobial molecules in primate as well as human, but as physiological protein. Its multiple functions extended to be one of immunogen could elicited autoimmune disorders. Purified camel lactoferrin (cLfs) from different Saudi camel clans were shown to be a potent immunogen when injected into rabbit. Four rabbit were subcutaneously immunized with different camel clans lactoferrin/Freunds adjuvant. Anti-cLfs potency titration was reach 1:32000 and did not significantly differences between different cLfs. The cross-reactivity level of different anti-Lfs were highly significant, specially between cLfs and bLf/hLf.

Keywords: Immunogenicity, lactoferrin, anti-lactoferrin, polyclonal antibody, milk, camel lactoferrin

DOI: 10.3233/HAB-180351

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

Authors: Thangaretnam, Krishna Priya | Sivam, Oviya | Ramanathan, Priya | Gopisetty, Gopal | Rajkuma, Thangarajan

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: CD99/MIC2gene product is a heavily glycosylated transmembrane protein which plays a major role in homotypic cell adhesion, apoptosis of double positive T cells and vesicular protein trafficking. It is over expressed in various cancers and has been considered as an ideal therapeutic target. The present study focused at developing monoclonal antibodies against the extracellular domain (ECD) of CD99 using hybridoma technology. MATERIALS AND METHODS: In order to generate monoclonal antibodies, the recombinant ECD of CD99 was used for immunizing the mice. Resulting hybridomas were screened through indirect ELISA. Clones which gave high absorbance …values were sub cloned by limiting dilution followed by isotype determination, IP, WB and FACS. The monoclonal antibody 547F2 4F12 was purified from culture supernatant using FPLC and further screened using IF. Finally, the antibodies were validated for specificity using siRNA knock-down. RESULTS: We were able to establish stable hybridoma clones secreting CD99 antibodies. The antibodies reacted with both the recombinant ECD as well as the wild type CD99 and their isotype’s were determined as IgM. CONCLUSION: Based on these results, we propose that the purified monoclonal antibody 547F2 4F12 could be possibly used for targeting tumors which over express CD99. Show more

Keywords: CD99, recombinant protein, antibody purification and validation

DOI: 10.3233/HAB-180350

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

Authors: Khosravi, Mohammad | Boroun, Fatemeh | Nemati, Mohammad

Article Type: Research Article

Abstract: BACKGROUND: The hypersensitivity reaction to penicillin is a public health problem. Immunological responses to penicillin and other beta-lactam antibiotics can be classified into immediate and non-immediate responses. The immediate hypersensitivity is mediated by IgE; however, the non-immediate sensitivity is facilitated by other isotypes of antibody or T lymphocytes. OBJECTIVE: This research detected the non-IgE antibody value against penicillin in allergic and normal people. METHODS: Thirty-eight samples from patients with positive or negative intradermal skin testing results of penicillin allergy were included in this study. The total antibody and IgM levels against penicillin G …were defined by in-house ELISA test. RESULTS: The results showed a significant (P < 0.05) elevation in total immunoglobulin and non-IgM anti-penicillin antibody of sensitive groups; however, the anti-penicillin IgM was significantly greater in non-sensitive peoples. CONCLUSIONS: Although the sensitized people to penicillin cannot be certainly detected with the total antibody, specific IgG and IgM value against penicillin, these values are good indicators for prediction of immediate and late response of the immune system to penicillin. Show more

Keywords: Penicillin, sensitivity, antibody, ELISA, human

DOI: 10.3233/HAB-180349

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

Authors: Mukherjee, Anubhab | Waters, Ariana K. | Babic, Ivan | Nurmemmedov, Elmar | Glassy, Mark C. | Kesari, Santosh | Yenugonda, Venkata Mahidhar

Article Type: Research Article

Abstract: Antibody drug conjugates (ADC’s) represent a promising and an efficient strategy for targeted cancer therapy. Comprised of a monoclonal antibody, a cytotoxic drug, and a linker, ADC’s offer tumor selectively, reduced toxicity, and improved stability in systemic circulation. Recent approvals of two ADC’s have led to a resurgence in ADC research, with more than 60 ADC’s under various stages of clinical development. The therapeutic success of future ADCs is dependent on adherence to key requirements of their design and careful selection of the target antigen on cancer cells. Here we review the main components in the design of antibody drug …conjugates, improvements made, and lessons learned over two decades of research, as well as the future of third generation ADCs. Show more

Keywords: ??

DOI: 10.3233/HAB-180348

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

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: 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: 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: 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