| dc.contributor | Zavala-Cerna, M.G., Facultad de Medicina, Universidad Aut�noma de Guadalajara, Guadalajara, Jalisco, Mexico; Mart�nez-Garc�a, E.A., Physiology Department, Instituto de Investigaci�n en Reumatolog�a Y del Sistema Musculoesquel�tico, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico; Torres-Bugar�n, O., Facultad de Medicina, Universidad Aut�noma de Guadalajara, Guadalajara, Jalisco, Mexico; Rubio-Jurado, B., Servicio de Hematolog�a, Hospital de Especialidades, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico; Riebeling, C., Unidad de Investigaci�n en Epidemiologia Cl�nica, Centro M�dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Guadalajara, Mexico, Facultad de Medicina, Universidad Nacional Aut�noma de Mexico, Guadalajara, Jalisco, Mexico; Nava, A., Unidad de Investigaci�n en Epidemiologia Cl�nica, Hospital de Especialidades, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico, Decanato Ciencias de la Salud, Universidad Aut�noma de Guadalajara, Guadalajara, Jalisco, Mexico, Servicio de Medicina Interna, �rea Investigaci�n, Reumatolog�a e Inmunolog�a, Hospital General de Occidente de la Secretaria de Salud Jalisco, Guadalajara, Jalisco, Mexico | |
| dc.description.abstract | Posttranslational modifications (PTMs) are defined as covalent modifications occurring in a specific protein amino acid in a time- and signal-dependent manner. Under physiological conditions, proteins are posttranslationally modified to carry out a large number of cellular events from cell signaling to DNA replication. However, an absence, deficiency, or excess in PTMs of a given protein can evolve into a target to trigger autoimmunity, since PTMs arise in the periphery and may not occur in the thymus; hence, proteins with PTMs never tolerize developing thymocytes. Consequently, when PTMs arise during cellular responses, such as inflammation, these modified self-antigens can be taken up and processed by the antigen-presenting cells (APCs). Autoreactive T cells, which recognize peptides presented by APCs, can then infiltrate into host tissue where the modified antigen serves to amplify the autoimmune response, eventually leading to autoimmune pathology. Furthermore, a PTM occurring in an amino acid residue can induce changes in the net charge of the protein, leading to conformational modifications in the tertiary and quaternary structure of the protein, especially interaction with human leukocyte antigen (HLA) molecules. Molecular mimicry (MM) was until now the prevailing hypothesis explaining generation of autoimmunity; nevertheless, experimental animal models need inflammation via infection or other immunogens to ensure autoimmunity; MM alone is not sufficient to develop autoimmunity. PTMs could arise as an additive factor to MM, which is required to start an autoimmune response. PTMs have been found to be present in different pathologic conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, and primary biliary cirrhosis. The aim of the present review is to expose protein posttranslational modifications and the evidence suggesting their role in the generation of autoimmunity. � 2014 Springer Science+Business Media. | |
