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

Authors: Shawky, Heba | El-Shenawy, Reem | Helmy, Naiera M.

Article Type: Research Article

Abstract: This study aimed to evaluate the prognostic value of baseline macrophage inflammatory protein (MIP)-1β /IL12p40 ratio for antiviral treatment outcome in HCV genotype 4 patients. METHODS: Sera of 450 treatment-naïve chronic HCV patients and 50 healthy individuals were collected. Liver transaminases, total bilirubin and albumin were biochemically tested, viral RNA was quantified, and circulating MIP-1β and IL-12p40 were estimated using human anti-MIP-1β and IL-12p40 antibodies in Sandwich ELISA. RESULTS : No difference was observed in the baseline chemokines levels between responders and relapsers, but the later had a …significantly higher MIP-1β /IL-12p40 ratio (P < 0.0001). Multivariate regression analysis of baseline characteristics showed that gender, age, viral load, albumin level and chemokine ratios can significantly predict treatment outcome (P = 0.0114, 0.0095, 0.042, 0.0004 and < 0.0001; respectively). Accordingly, a predictive threshold of baseline chemokine ratio was calculated and it showed an AUC of 0.6917 (P = 0.0108; 95% CI: 0.5566 to 0.8268). The calculated threshold for predicting virologic response was 8.245, with positive and negative predictive values of 92.98% and 100%; respectively. The chemokine ratios had significant correlations with liver transaminases in treated groups whether pre or post-treatment. CONCLUSION: Baseline MIP-1β /IL-12p40 ratio represents a non-invasive prognostic biomarker that would provide shorter treatment duration and minimizes the emergence of drug-resistant variants in HCV genotype 4-patients. Show more

Keywords: Chronic HCV, DAA therapy, chemokine profile, prognostic biomarker, SVR12, treatment failure

DOI: 10.3233/HAB-211504

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Vafaee, Reza | Tavirani, Mostafa Rezaei | Tavirani, Sina Rezaei | Razzaghi, Mohammadreza

Article Type: Research Article

Abstract: There are many documents about benefits of exercise on human health. However, evidences indicate to positive effect of exercise on disease prevention, understanding of many aspects of this mechanism need more investigations. Determination of critical genes which effect human health. GSE156249 including 12 gene expression profiles of healthy individual biopsy from vastus lateralis muscle before and after 12-week combined exercise training intervention were extracted from gene expression omnibus (GEO) database. The significant DEGs were included in interactome unit by Cytoscape software and STRING database. The network was analyzed to find the central nodes subnetwork clusters. The nodes of prominent …cluster were assessed via gene ontology by using ClueGO. Number of 8 significant DEGs and 100 first neighbors analyzed via network analysis. The network includes 2 clusters and COL3A1, BGN, and LOX were determined as central DEGs. The critical DEGs were involved in cancer prevention process. Show more

Keywords: Gene, exercise, cancer, network, gene ontology

DOI: 10.3233/HAB-210454

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-6, 2021

Authors: Baker, David | Asardag, A. Nazli | Quinn, Olivia A. | Efimov, Alex | Kang, Angray S.

Article Type: Research Article

Abstract: Multiple sclerosis is the major demyelinating autoimmune disease of the central nervous system. Relapsing MS can be treated by a number of approved monoclonal antibodies that currently target: CD20, CD25 (withdrawn), CD49d and CD52. These all target potentially pathogenic memory B cell subsets and perhaps functionally inhibit pathogenic T cell function. These consist of chimeric, humanized and fully human antibodies. However, despite humanization it is evident that all of these monoclonal antibodies can induce binding and neutralizing antibodies ranging from < 1% to over 80% within a year of treatment. Importantly, it is evident that monitoring these …allow prediction of future treatment-failure in some individuals and treatment cessation and switching therefore potentially limiting disease breakthrough and disability accumulation. In response to the COVID-19 pandemic and the need to avoid hospitals, shortened infusion times and extended dose intervals have been implemented, importantly, subcutaneous delivery of alternative treatments or formulations have been developed to allow for home treatment. Therefore, hospital-based and remote monitoring of ADA could therefore be advantageous to optimize patient responses in the future. Show more

Keywords: Multiple sclerosis, immunotherapy, biologic disease modifying therapies, anti-drug antibodies

DOI: 10.3233/HAB-210453

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Saravani, Khadijeh | Salarzaei, Morteza | Parooie, Fateme

Article Type: Systematic Review

Abstract: INTRODUCTION: Metastatic or recurrent colorectal cancer (MRCRC) has a poor prognosis. The aim of the present meta-analysis was to assess the prevalence of different subtypes of KRAS mutation and BRAF mutation in metastatic CRC patients, and evaluate the relationship between the tumor sidedness and prevalence of KRAS and BRAF mutation. METHODS: We searched MEDLINE/PubMed, the Cochrane Library, and ClinicalTrials.gov from January 2010 to July 2020. The data were extracted independently according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The statistical analysis was done using STATA and Meta-Disk 1.4 applications. RESULTS: …Overall, 6699 colorectal cancer patients were included. KRAS and BRAF mutation was reported in 28% and 6% of patients, respectively. The overall prevalence of right primary and left primary metastatic CRC patients with mutated KRAS was 40% and 60%. However, the prevalence BRAF mutated right primary and left primary metastatic CRC patients was 37% and 63%. The overall HR was 2.38 for patients with metastatic CRC who had a mutated type of KRAS. Our study showed a mean overall survival of 35.4 month for KRAS mutant and a 10.12 month survival for BRAF mutant patients with metastatic colorectal cancer patients. CONCLUSION: The prevalence of KRAS and BRAF mutations varied significantly according to the location of the tumor. BRAF mutations are more commonly found in metastatic colorectal cancers on the right side. Liver was the most common site of metastases in patients with mutant KRAS and the mortality of patients with mutant KRAS was 2.3 times higher than the patients with wild types. These results help to better describe the population of mCRC patients and can have implications for improving and organizing anti-EGFR therapies. Further research is needed to assess differences in survival through mutation status and primary tumor location. Show more

Keywords: KRAS mutation, BRAF mutation, colorectal cancer, metastatic

DOI: 10.3233/HAB-210451

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Beksac, Mehmet Sinan | Donmez, Hanife Guler

Article Type: Research Article

Abstract: This study aimed to investigate the association of increased C-Reactive Protein (CRP) and hypocomplementemia with risk factors for thrombosis such as Factor V Leiden (FVLP) and Prothrombin G20210A polymorphisms (PP), increased Activated Protein C Resistance (APCR) and decreased anti-thrombin III (ATIII) activity in women who have metabolic (MTHFR polymorphisms) and immunological risk factors (autoimmune antibody positivity, autoimmune disorders, and chronic inflammatory diseases). All patients (n = 197) were evaluated in terms of risk factors for thrombosis including FVLP, PP, increased APCR, and decreased ATIII activity as well as CRP and complement (C) 3 and …C4 levels within a framework of preconceptional care program. Patients with high CRP levels together with hypocomplementemia were included to the study group (n = 13), while women with normal levels of CRP, C3, and C4 were accepted as controls (n = 184). Decreased ATIII activity was found to be statistically more frequent in the study group compared to controls (p = 0.036). There were no significant differences between the study and control groups in terms of the presence of FVLP, PP and increased APCR (p = 0.386, p = 0.462, p = 0.625, respectively). Decreased ATIII activity should be the concern of preconceptional and antenatal care programs in risky patients with increased CRP levels and hypocomplementemia in order to prevent placental inflammation related gestational complications. Show more

Keywords: Obstetrical complications, placental inflammation, pregnancy, C-reactive protein, complement, thrombosis

DOI: 10.3233/HAB-210452

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-6, 2021

Authors: Ghaemi, Farahnaz | Fateh, Abolfazl | Sepahy, Abbas Akhavan | Zangeneh, Mehrangiz | Ghanei, Mostafa | Siadat, Seyed Davar

Article Type: Research Article

Abstract: BACKGROUND: Type 2 diabetes as the most prevalent metabolic disorder, is one of the major causes of morbidity and mortality worldwide. Recent studies suggest that body microbiota may play a role in developing metabolic disorders including type 2 diabetes. The objective of the present study was to investigate the blood microbiota composition in Iranian pre-diabetic and type 2 diabetic patients compared to healthy individuals. METHODS: Blood samples were taken after 12-h fasting from 90 participants, 30 healthy individuals, 30 type 2 diabetes patients and 30 pre-diabetic participants. The buffy coat layer separated by centrifugation at 800 …and DNA was extracted using a column-based method. Composition and load of blood microbiota was evaluated by real-time PCR method using genus specific 16S rRNA primers. RESULTS: The load of Akkermansia, and Faecalibacterium was higher in normal volunteers compared to pre-diabetic and type 2 diabetes group (p < 0.05). The load of Bifidobacterium was higher in normal volunteers compared to type 2 diabetes patients (p = 0.02). In contrast, the load of Lactobacillus and Escherichia coli was higher in pre-diabetics and type 2 diabetes patients compared to normal volunteers (p < 0.05). The load of Bacteroides fragilis was not statistically different between studied groups but it was higher in males compared to female group (p = 0.04). the load of other bacteria was not significantly different between male and female participants. CONCLUSION: There is difference between microbiota composition in white blood cells of pre-diabetic and type 2 diabetes patients compared to healthy people. Determination of blood microbiota pattern may have a role in diagnosis and preventive of type 2 diabetes in a certain population. For more clarification about correlation between blood microbiota and type 2 diabetes, larger studies with more participants in different ethnical populations is suggested. Show more

Keywords: Microbiota, type 2 diabetes, pre-diabetes

DOI: 10.3233/HAB-210450

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-6, 2021

Authors: Bqain, Mariam | Efimov, Alex | Baker, David | Kang, Angray S.

Article Type: Research Article

Abstract: PURPOSE OF THE REVIEW: Here we critically evaluate the literature on immunotherapy failure in inflammatory bowel disease patients. In particular anti-drug antibody production, and subsequently loss of response as the primary cause of immunotherapy failure in IBD patients. The benefits of shifting from the “standard” empirical dose escalation approach to therapeutic drug monitoring with anti-TNFα therapy is explored. RECENT FINDINGS: The American Gastroenterology Association and British Society of Gastroenterology both currently recommend the use of reactive therapeutic drug monitoring to guide treatment, following loss of response in inflammatory bowel disease patients with active …disease. However, further research is required to prove the efficacy of a proactive therapeutic drug monitoring approach alone in remitted IBD patients. SUMMARY: A combination of personalised monitoring approach for anti-drug antibodies and therapeutic drug monitoring could provide beneficial treatment outcome for people with inflammatory bowel disease by predicting drug failure prior to clinical symptoms and allowing timely switching to an alternative drug. Show more

Keywords: Inflammatory bowel disease, immunotherapy, biologic disease modifying therapies, anti-drug antibodies

DOI: 10.3233/HAB-210449

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Boluri, Ahmad | Khazaei, Hosseinali | Sargolzaei, Narjes | Miri, Hanie Olfat | Khazaei, Bahman

Article Type: Research Article

Abstract: BACKGROUND: Interleukin (IL)-17 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-17 levels in unstable angina are lacking. The aim of our study is to evaluate and compare the IL-17 levels in unstable angina (UA) cases before and after treatment. METHODS: This cross-sectional study was performed from July to October 2018 in Ali Iben-abitaleb heart center, Zahedan, Iran. 48 patients with UA in the age range of below 50 years entered the study. All demographic, past medical history, physical …examination, electrocardiogram (EKG or ECG), and transthoracic echocardiogram (TTE) data were collected. Serum level of IL-17 was measured using enzyme-linked immunosorbent assay (ELISA) method. In all the tests, P < 0.05 was considered as statistically significant. All data analyses were performed using the SPSS 13.0 software (SPSS Inc., Chicago, Illinois, USA). RESULTS: In this study, 48 UA patients, including 34 women and 16 men with a mean age of 56.60 years were included in the study. The mean serum level of interleukin 17 after treatment (65.13 ± 53.29 pg/dl) was significantly lower than Its level before treatment (94.89 ± 51.25 pg/dL) (P < 0/05). CONCLUSION: Our findings point towards a role of inflammation in the form of increased activity of IL-17 in UA patients and thus suggest that IL-17-driven inflammation may play a role in the promotion of clinical instability in patients with coronary artery disease. Show more

Keywords: Interleukin-17, stable angina, unstable angina

DOI: 10.3233/HAB-210446

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-5, 2021

Authors: Kalvandi, Gholamreza | Shahramian, Iraj | Farmany, Abbas | Yadegari, Shirin | Parooie, Fateme

Article Type: Research Article

Abstract: BACKGROUND: Celiac disease is a common gastrointestinal autoimmune disorder. Studies have shown that the prevalence of tooth decay is high in patients with celiac disease. This study was performed to evaluate the serology of celiac disease in children with dental caries. METHODS: Children aged 3 to 12 years who referred to the dental clinic with enamel caries were included in the study. Celiac disease was assessed by measuring serum IgA levels and anti-TTG (Anti TTG (IgA)) antibodies. Then, by analyzing the collected data, the prevalence of celiac disease in children with dental caries and its relationship …with various variables were investigated. RESULTS: 120 children, 56 girls (46.7%) and 64 boys (53.3%) with dental caries were involved in this study. The positive celiac serology rate of studied population was 14 (11.6%). Based on the results of this study, a significant relationship was obtained between maternal education, sex and place of residence and celiac disease (p < 0.05). There were no significant relationships between celiac positive serology in children with dental caries, the number of decayed teeth, and breastfeeding (p > 0.05). CONCLUSION: The present study showed that dental caries, might be a red flag indicating possible celiac disease and prevent its complications. On the other hand, pediatricians and dentists should be aware of the oral symptoms of celiac disease. Further studies are needed to plan screening for children with celiac disease. Show more

Keywords: Celiac disease, tooth decay, prevalence

DOI: 10.3233/HAB-210445

Citation: Human Antibodies, vol. Pre-press, no. Pre-press, pp. 1-5, 2021