Identification of conformational epitopes on fragment crystallizable region of human Immunoglobulin G by immunoinformatic

Background: Immunoglobulins are a group of proteins have important role in defense against microorganisms. Human immunoglobulins are divided into five classes: IgA, IgM, IgD, IgE and IgG. Immunoglobulin G (IgG) is the highest abundant antibody in serum and extravascular fluids. The extent of serum IgG is related to severity of several diseases such as infections, so IgG has great diagnostic worth. Accurate measurement of IgG, needs exact and sensitive diagnostic instruments such as human IgG- specific monoclonal antibodies. Moreover, targeting of IgG has been useful in treatment of a number of diseases. According to experimental studies the Fc region of human IgG is highly immunogenic. Immunoinformatic is a division of immunology uses the computational biology for more precise diagnosis of diseases. The aim of this study was determination of conformational epitopes in the fragment of crystallizable (Fc) fragment of human IgG by immunoinformatic. Methods: The amino acid residues and third structure of reference human IgG were found in protein data bank (PDB). Second IgG structure was defined by Phyre2 software (http://www.sbg.bio.ic.ac.uk/~phyre2/). Conformational epitopes of the Fc fragment in human IgG were specified by ElliPro (http://tools.iedb.org/ellipro/) and DiscoTope (http://www.cbs.dtu.dk/services/DiscoTope) softwares. Results: In this study two conformational epitopes (one in constant heavy chain 2 (CH2) domain and another one common between CH2 and CH3 domains) sited in Fc fragment of human IgG were determined by ElliPro software. Also, two conformational epitopes (Both common between CH2 and CH3 domains) located to Fc fragment of human IgG were determined by DiscoTope software. Conclusion: In this study a number of conformational epitopes located to Fc fragment of human IgG were determined by two immunoinformatic softwares (ElliPro and DiscoTope). The epitopes recognized by both softwares were situated in CH2, CH3 or both of these domains in the human IgG heavy chain. Thus, it seems that CH2 and CH3 domains of Fc region in human IgG are highly immunogenic. Moreover, ElliPro and DiscoTope softwares can be useful tools for identification of epitopes located to Fc fragment of human IgG

Suppression of Gelatinase Activity in Human Peripheral Blood Mononuclear Cells by Verapamil

Objective: Gelatinases are a large group of proteolytic enzymes that belong to the matrix metalloproteinases (MMPs). MMPs are a broad family of peptidases, which proteolyse the extracellular matrix and have an important role in inflammation. Verapamil is a calcium channel blocker extensively used in the treatment of numerous cardiovascular diseases such as arrhythmia and hypertension. The anti-tumor and anti-inflammatory effects of verapamil have also been shown. In this study, the effect of verapamil on gelatinase activity in human peripheral blood mononuclear cells (PBMCs) has been assessed in vitro. Materials and Methods: In this experimental study, PBMCs from healthy adult volunteers were isolated by ficoll-hypaque-gradient centrifugation. The cells were then cultured in complete RPMI-1640 medium and after that incubated with different concentrations of verapamil (0–200 μM) in the presence or absence of phytoheamagglutinin (PHA) (10 μg/ml) for 48 hours. The gelatinase A (MMP-2)/gelatinase B (MMP-9) activity in cell-conditioned media was then evaluated by gelatin zymography. Statistical comparisons between groups were made by analysis of variance (ANOVA). Results: Verapamil significantly decreased the MMP-2/MMP-9 activity in human PBMCs after 48 hours incubation time compared with untreated control cells. The association was dose-dependent. Conclusion: In this study verapamil exhibited a dose-dependent inhibitory effect on gelatinase A and gelatinase B activity in human PBMCs. It seems that the anti-inflammatory properties of verapamil may be in part due to its inhibitory effects on gelatinase activity. Regarding the beneficial effects of MMPs- inhibitors in the treatment of some cardiovascular diseases, the positive effect of verapamil on such diseases may be in part due to its anti-MMP activity. Verapamil with its inhibitory effects on gelatinases activity may be a useful MMP-inhibitor. Given the beneficial effect of MMP-inhibitors in some cancerous, inflammatory and autoimmune disorders, it seems likely that verapamil could also be used to treat these diseases

In Silico Prediction of Continuous Epitopes on Human immunoglobulin Light Chains

Background & Objective: Immunoglobulins (Igs) have a vital role in body protection against germs. Igs contain heavy and light chains. Ig light chains consist of two isotypes: Kappa and lambda. Remarkable alterations in kappa to lambda proportion could occur in monoclonal growth of malignant B cells. Anti-human light chain monoclonal antibodies (MAbs) have medical implication in diagnosis and immunotherapy of B-cell proliferative disorders. In current study, prediction of continuous epitopes in constant part of human Ig light chain by immunoinformatics is explained. Materials & Methods: Amino acid sequence and third structure of reference human IgG light chain was obtained in PDB database. Second IgG structure was identified by Phyre 2 software. Continuous epitopes of Ig light chains were delineated by Bepipred and Ellipro software programs. Results: Four continuous epitopes situated to constant domain of human Ig light chain were predicted by Bepipred software. These continuous epitopes were located at amino acid sequences 110-130, 150-160, 160-175 and 180-205 of Ig light chain. The prominent epitope was sited at amino acids 160-175. Also, one continuous epitope situated in 198-203 amino acid sequences was predicted by Ellipro software. Conclusion: In present study several continuous epitopes sited to constant part of human Ig light chain were determined. These epitopes are valuable for making specific monoclonal anti- Ig light chain antibodies and could have plausible implication in generation of specific diagnostic kits for human Ig light chain, monitoring the monoclonal light chain diseases, treatment of associated B cell malignancies and epitope mapping of Ig light chain

SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation

Since the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a growing body of evidence indicates that besides common COVID-19 symptoms, patients may develop various neurological manifestations affecting both the central and peripheral nervous systems as well as skeletal muscles. These manifestations can occur prior, during and even after the onset of COVID-19 general symptoms. In this Review, we discuss the possible neuroimmunological mechanisms underlying the nervous system and skeletal muscle involvement, and viral triggered neuroimmunological conditions associated with SARS-CoV-2, as well as therapeutic approaches that have been considered for these specific complications worldwide

SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation

Since the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a growing body of evidence indicates that besides common COVID-19 symptoms, patients may develop various neurological manifestations affecting both the central and peripheral nervous systems as well as skeletal muscles. These manifestations can occur prior, during and even after the onset of COVID-19 general symptoms. In this Review, we discuss the possible neuroimmunological mechanisms underlying the nervous system and skeletal muscle involvement, and viral triggered neuroimmunological conditions associated with SARS-CoV-2, as well as therapeutic approaches that have been considered for these specific complications worldwide