The clinical significance of posttranslational modification of autoantigens

Abstract

Aim. To analyze the influence of age on the performance of a planning and organization task, two skills included in the executive functions. Subjects and methods. Performance of the task 'Mexican pyramid' from the Evaluación Neuropsicológica Infantil (ENI) were analyzed on 239 school age children from México and Colombia, distributed in six age groups. Five measures were analyzed: number of correct designs, number of movements per design and execution time in the correct designs, number of correct designs built with the minimum of movements and its execution time. Results. There was a significant effect of age on the five measures. Comparison between groups showed that younger children (5 to 6 years old) had a smaller number of correct designs, while children from 5 to 8 years old need more movements. Execution time showed a greater number of differences between groups. Analyzing the 11 items of the task, it was evident that difficulty level is related with the number of movements and the novelty of rules. Conclusions. Our results suggest that accuracy of performance, the number of moves as well as the speed of performance are useful markers of the development of the executive functions. Our results support the notion that the development of planning and organization; is fast in the first years of the school age, and it slows down on adolescence. " 2008, Revista de Neurología.",,,,,,,,,"http://hdl.handle.net/20.500.12104/45083","http://www.scopus.com/inward/record.url?eid=2-s2.0-48249135773&partnerID=40&md5=5cc5494868e4b3c399402f4426ef78fc",,,,,,"2",,"Revista de Neurologia",,"61

70",,"47",,"Scopus

WOS",,,,,,"Development; Execution time; Executive functions; Organization; Planning",,,,,,"The effect of age in a planning and arranging task ('Mexican pyramid') among schoolchildren [Efecto de la edad en una tarea de planificación y organización ('pirámide de México') en escolares]",,"Article" "46833","123456789/35008",,"Zavala-Cerna, M.G., Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, Mexico; Martínez-García, E.A., Physiology Department, Instituto de Investigación en Reumatología Y del Sistema Musculoesquelético, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico; Torres-Bugarín, O., Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, Mexico; Rubio-Jurado, B., Servicio de Hematología, Hospital de Especialidades, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico; Riebeling, C., Unidad de Investigación en Epidemiologia Clínica, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Guadalajara, Mexico, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Guadalajara, Jalisco, Mexico; Nava, A., Unidad de Investigación en Epidemiologia Clínica, Hospital de Especialidades, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico, Decanato Ciencias de la Salud, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, Mexico, Servicio de Medicina Interna, área Investigación, Reumatología e Inmunología, Hospital General de Occidente de la Secretaria de Salud Jalisco, Guadalajara, Jalisco, Mexico",,"Zavala-Cerna, M.G.

Martinez-García, E.A.

Torres-Bugarin, O.

Rubio-Jurado, B.

Riebeling, C.

Nava, A.",,"2014",,"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.