A Nature Research Journal.
Journal of Autoimmunity
Novel single-cell profiling technologies have delineated the cellular and molecular landscapes that dominate the joints in rheumatoid arthritis and the skin and kidneys in systemic lupus erythematosus, shedding light on potential pathogenic mechanisms. Der, E. Arazi, A. Zhang, F. Spitzer, M. Cell , — Chen, H. Download references. Correspondence to Navin Varadarajan or Chandra Mohan. The MHC class I binding area is closed, limiting the length of the presented peptides to 8—10 amino acids [ 28 ], however, MHC class II binding site is open and led peptides with 14—18 aa in length [ 28 ], but under certain conditions shorter peptides can be presented [ 29 ].
Autoimmunity is defined as a condition of loss of immune tolerance to self-antigens causing an autoreactive immune T and B cells that attack own organs provoking an aseptic inflammation and comprised more than 80 chronic diseases characterized by inflammatory reactions that can either be systemic or organ specific [ 30 ] and no cure exist for the majority autoimmune diseases and the treatment is based by control disease symptoms [ 31 ]. The early event in autoimmunity is the presentation of self-antigen derived peptides in complex with MHC class II to self-reactive T cells in an inflammatory environment where antigen-presenting cell, dendritic cell mainly, is activated and drives co-stimulation and development of pathogenic autoreactive T cell and autoantibodies, playing a critical role in breaking tolerance to self during an autoimmune disease, leading tissue and organ damage [ 31 , 32 ], produced by susceptible and aberrant genes, environment exposure, and failed immune regulation [ 30 ].
Dendritic cells are the responsible for the initiation of primary T cell responses imprinting the phenotype Th1, Th2, Th17, Treg population in response to environmental signals mediating the breach of T cell tolerance in many autoimmune conditions [ 31 ] involved in the activation of other autoreactive B cells [ 33 ].
Indeed, T cell help for antigens and can lead the activation of B cells that recognized the foreign antigen but also cross-react with self-antigen [ 34 ] producing and autoimmune disease. T cells, for example, are important for the pathogenesis of rheumatoid arthritis RA , particularly in the initial phase of autoimmune response, inducing the joint inflammation of the joints [ 3 ].
Synovial macrophages and fibroblast in a stress aseptic or septic injury released proinflammatory cytokines causing the production and release of IL that provokes the overproduction of RANK by fibroblast and macrophages. The continued presence of RANK, produce the active form of osteoclast, reabsorbing bone. Autoantigens can be defined as antigens that can be assumed to be targeted in an autoimmune disease [ 28 ] by the production autoantibodies by autoreactives B cells. Indeed, autoantibody-producing B cell originated from T cell responses to foreign antigens thought molecular mimicry between microbial antigens and self-antigens [ 33 ].
The literature describes many autoantigens for each autoimmune disease. Type 1 diabetes mellitus T1DM is a metabolic disease that is explained as an autoimmune disease in which the B-cells in the Langerhans islands of pancreas are destroyed by autoreactive T and B cells resulting in a null production of insulin [ 28 ]. Zinc transporter 8 protein, pancreatic and duodenal homeobox 1, chromogranin A, islet amyloid polypeptide are new discovered autoantigens that explain the pathogenesis of T1DM [ 36 ].
Systemic lupus erythematosus SLE is an autoimmune disease that affects connective tissue [ 37 , 38 ], involved multiple systems, organs and autoantigens [ 38 ]. Autoantigens acidic ribosomal phosphoprotein P0 -4, acidic ribosomal phosphoprotein P0 , DNA topoisomerase 1 full length -1, and U1-SnRNP, were founded in clinical tests and are using as markers for clinical diagnoses [ 38 ]. Rheumatoid arthritis RA is a chronic inflammatory disease with a strong autoimmune component that affect bones and joints with the concomitant destruction, associated with adverse morbidity, mortality, and socioeconomic consequences [ 39 ].
Molecular mechanisms of autoimmunity.
Autoantibodies such as rheumatoid factors RFs and anti-citrullinated protein antibodies ACPAs founded in serum samples obtained years before the onset of clinical disease [ 40 , 41 ]. Autoantigens may cause a self-reactivity of T and B cells by dysregulation of homeostasis of immune response acting as a trojan horses harming own body producing an autoimmune disease. In silico tools have provided a powerful means of understanding the contribution of the human microbiome to health and disease opening a great field for oral immunologist.
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In the era of computer trojan horse, microbial epitopes with high similarities in sequence and structure with the host, can act as little sequences for the evasion of host immune system, even more, this trojans may cause a T and B reactive cells provoking an immune response for the microbial elimination and the origin of an autoimmune disease [ 43 ]. Systemic lupus erythematosus SLE is an prototype of autoimmune disease, affecting the connective tissue [ 44 ], with a great spectrum of clinical symptoms such as joints, kidneys, skin, to other manifestation, in fact, SLE is a nonpreventable disease and may be life-threatening [ 45 , 46 ].
This protein has a 6 aminoacids aa similarity against VWA domain-containing protein of Prevotella denticola Table 1. This protein has a 7 aa similarity against Bacillus cereus Table 1. Aquaporin 4 is an integral membrane protein that conducts water through cell membrane founded in nervous system. It is presented as autoantingen in neuromyelitis optica, an autoimmune disease consisting of a chronic inflammation and demyelination of optical nerve and spinal cord.
This protein has similarities against glycerol uptake facilitator protein 2 of Streptococcus pneumoniae , MIP family channel protein of Prevotella oralis and MIP family channel protein of Enterococcus faecalis Table 2. Glycerol uptake facilitator protein 2 is a putative nonselective transport channel in the inner membrane of bacterium [ 49 ] and MIP family channel is a transmembrane protein transporting small molecules [ 50 ].
Both proteins are in external side of microbial cell membrane been more efficient form antibody-epitope complex. Glutamate decarboxylase 2 is an autoantigen related in Stiff-Person syndrome, an autoimmune disease that affects nervous system. Glutamate decarboxylase of Enterococcus spp.
Type 1 diabetes is an autoimmune disease in which the B-cells in the Langerhans islands of pancreas are destroyed by T and B reactive cells lacking the insulin production [ 28 ], affecting children and latent autoimmune disease of adults [ 51 ].
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One of characteristics of this disease is the recognition of beta cell proteins as autoantigens such as preproinsulin GAD65, islet antigen 2 IA-2 , ZnT8, nonspecific islet cell autoantigens ICAs , imogen 38, pancreatic duodenal homeobox factor 1, chromogranin A, islet specific glucosephosphatase catalytic subunit-related protein, heat shock protein 60 and islet cell antigen IA-2, possess 6 aa with similar characteristics with LysM peptidoglycan-binding domain-containing protein of Streptococcus mitis Table 3 that is present to bind noncovalently to peptidoglycan and chitin in cell wall [ 52 ].
Thyroiditis is an autoimmune disease that destroys thyroid cells by reactive T and B cells.
Discovery may help explain why women get autoimmune diseases far more often than men
This disease is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis. The pathology of thyroiditis involves the formation of antithyroid antibodies that attack thyroid tissue, causing progressive fibrosis [ 53 ]. Ku is an abundant protein in the body with multiple functions as replication, transcription and cell signaling [ 54 ].
Pilin isopeptide linkage domain protein of E.
Prevotella sp. Myasthenia gravis is an autoimmune disease that attacks neuromuscular junction where synapsis occurs between nerves and muscles causing muscle weakness in patients [ 55 ]. Autoantibodies such as muscle-specific tyrosine kinase MUSK , acetylcholine, agrin and low-density lipoprotein receptor—related protein 4 LPR4 have been described in the literature [ 56 , 57 ]. Table 5. This lactobacillus protein is present in cell wall in gram positives and negatives associated to penicillin-binding proteins [ 58 ].
Lactobacillus spp. Autoimmune hepatitis is a chronic and progressive inflammation of the liver from an unknown cause, whose pathology is explained by the failure of immune tolerance in a genetically susceptible individual leading to a reactive T-cell mediated inflammation caused by various environmental triggers including infections, medications, and toxins [ 62 ]. FTCD epitopes have similarities with glutamate formimidoyltransferase of Porphyromonas gingivalis , formimidoyltetrahydrofolate cyclodeaminase of Fusobacterium nucleatum and glutamate formimidoyltransferase of Streptococcus spp Table 7.
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