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The Clinical Significance of Posttranslational Modification of Autoantigens

Clinical Reviews in Allergy & Immunology volume 47, pages 73–90 (2014)Cite this article

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.

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Acknowledgments

We would like to thank Martha Cristina Fernandez-Chairez for her contribution to image creation and editing.

Conflict of Interest

The authors declare that there is no conflict of interests regarding the publication of this paper.

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Affiliations

  1. Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, Mexico

    Maria G. Zavala-Cerna & Olivia Torres-Bugarín

  2. Physiology Department, Instituto de Investigación en Reumatología y del Sistema Musculoesquelético, CUCS, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico

    Erika A. Martínez-García

  3. Servicio de Hematología y Unidad de Investigación en Epidemiologia Clínica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico

    Benjamín Rubio-Jurado

  4. Unidad de Investigación en Epidemiologia Clínica, Unidad Médica de Alta Especialidad Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Guadalajara, Mexico

    Carlos Riebeling

  5. Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Guadalajara, Jalisco, Mexico

    Carlos Riebeling

  6. Unidad de Investigación en Epidemiologia Clínica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico

    Arnulfo Nava

  7. Decanato Ciencias de la Salud, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, Mexico

    Arnulfo Nava

  8. Servicio de Medicina Interna, Área Investigación, Reumatología e Inmunología, Hospital General de Occidente de la Secretaria de Salud Jalisco, Guadalajara, Jalisco, Mexico

    Arnulfo Nava

Authors
  1. Maria G. Zavala-Cerna
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  2. Erika A. Martínez-García
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  3. Olivia Torres-Bugarín
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  4. Benjamín Rubio-Jurado
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  5. Carlos Riebeling
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  6. Arnulfo Nava
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Correspondence to Arnulfo Nava.

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Zavala-Cerna, M.G., Martínez-García, E.A., Torres-Bugarín, O. et al. The Clinical Significance of Posttranslational Modification of Autoantigens. Clinic Rev Allerg Immunol 47, 73–90 (2014). https://doi.org/10.1007/s12016-014-8424-0

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Keywords

  • Posttranslational modifications
  • Rheumatoid arthritis
  • Citrullination
  • Systemic lupus erythematosus
  • Celiac disease
  • Primary biliary cirrhosis
  • Thrombophilia