Tehran University Medical Journal

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.

Behçet's disease (BD), also known as the Silk Road disease, is a multisystemic and rare inflammatory disorder primarily prevalent in populations along the Mediterranean Sea. Today, BD is defined as a crossroad between autoimmune and auto-inflammatory syndromes. Variety of syndromes including mucocutaneous manifestations such as oral and genital ulcers, papulopustular lesions and erythema nodosum as well as ocular, vascular, gastrointestinal and nervous system occur. The disease etiology has not yet been elaborated, though researchers have reported several reasons that can increase the likelihood of the disease occurrence including a genetic factor, human leukocyte antigen HLA-B51 (B51) antigen, infectious conditions such as herpes simplex virus (HSV), those involved in inflammatory and autoimmune conditions such as imbalance of various cytokines and immune cells levels as well as existence of various gene variants. Among the various immuno dysfunctions that are found in BD, patients have increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin-10 (IL-10). Since vasculitis and tissue damage is usually seen with Behcet disease, unusual concentrations of chemokine and adhesion molecules can also help us understand the causes of disease. Among the functional deficiencies of the immune system, increased concentrations of neutrophils and monocytes are of importance leading to an increase in reactive oxygen species (ROS). Behcet's disease has common characteristics with some immune-mediated diseases such as systemic lupus erythematosus (SLE), psoriasis, ankylosing spondylitis, and inflammatory bowel disease (IBD), which suggests that they may share similar etiologies and genes. Genetic and epigenetic modulations have also been proposed as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to the adverse function of these cells. The positive replies to classical immunosuppressive agents like cyclosporine and azathioprine and participation of autoantigens at the beginning of the illness are the chief BD features that reflect the autoimmune nature of the disorder. This review article attempts to introduce the BD disease and its contributing factors with emphasis on the role of different cells and cytokines based on updated studies.