Arnulfo Nava

The Clinical Significance of Posttranslational Modification of Autoantigens

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.

Rosuvastatin Treatment is Associated with a Decrease of Serum Oxidised Low-Density Lipoprotein/Beta2-Glycoprotein I Complex Concentration in Type 2 Diabetes

Aims To evaluate the effect of rosuvastatin on oxidised lowdensity lipoprotein/beta2-glycoprotein I (oxLDL/β 2 GPI) complex concentration in type 2 diabetes mellitus. Methods Open label 2:1 assignment of consecutive diabetic patients into oral rosuvastatin (10 mg daily for six weeks) arm or observational arm with measurements of serum oxLDL/ β 2 GPI complexes, nitric oxide metabolites, asymmetric dimethyl arginine, nitrotyrosine alongside routine biochemistry at baseline and end of study in all patients. Results After rosuvastatin treatment the mean serum concentration of oxLDL/β 2 GPI decreased from 0.79±0.49 units/mL to 0.53±0.36 units/mL (p<0.001). The decrease was statistically independent from the decrements of mean cholesterol, LDL and triglyceride concentrations (p<0.001) but probably dependent on the decrement of nitrate (p<0.001). Conclusion In type 2 diabetes, treatment with rosuvastatin was associated with a significant reduction of serum concentrations of oxLDL/β 2 GPI complexes, which is in further support of the already proposed effects of the drug on the oxidative metabolism of lipids and/or LDL. The oxLDL/β 2 GPI complex may represent a surrogate marker of oxidative stress in type 2 diabetes. Br J Diabetes Vasc Dis 2010;10:292-299.

Patogenia de las miopatías inflamatorias idiopáticas

The inflammatory myopathies, commonly described as idiopathic, are a group of acquired diseases characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical and immuno-pathological features, three major diseases can be identified: dermatomiositis (DM), polymyositis (PM) and inclusion body myositis (IBM). Immunopathogenesis mechanisms are crucial for discriminating between the three different subsets of inflammatory myopathies. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens. This article summarizes the main immunopathological markers. The impact of this new knowledge must be defined in relation to potential therapeutic targets for idiopathic inflammatory myopathies.