Immune response to chemically modified proteome

Abstract

Both enzymatic and nonenzymatic PTMs of proteins involve chemical modifications. Some of these modifications are prerequisite for the normal functioning of cell, while other chemical modifications render the proteins as "neo-self" antigens, which are recognized as "non-self" leading to aberrant cellular and humoral immune responses. However, these modifications could be a secondary effect of autoimmune diseases, as in the case of type I diabetes, hyperglycemia leads to protein glycation. The enigma of chemical modifications and immune response is akin to the "chick-and-egg" paradox. Nevertheless, chemical modifications regulate immune response. In some of the well-known autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, chemically modified proteins act as autoantigens forming immune complexes. In some instances, chemical modifications are also involved in regulating immune response during pathogen infection. Further, the usefulness of proteomic analysis of immune complexes is briefly discussed.

Elevated Transglutaminase Activity Triggers Angiotensin Receptor Activating Autoantibody Production and Pathophysiology of Preeclampsia

“…One of the commonly accepted causes for autoantibody production is PTM of proteins to generate neoantigens . Celiac disease is the most common autoimmune disease caused by TG2‐mediated PTM.…”

“…However, this possibility was not supported by epidemiological data that failed to show a correlation between PE and prior parvovirus infection . A commonly considered mechanism for an autoimmune response is posttranslational modification (PTM), resulting in the creation of a neoantigen that is recognized as nonself by the immune system . A large percentage of proteins in the body are targets of PTM, and it is now clear that some of these modifications create new antigens that stimulate an autoimmune response .…”

“…20 A commonly considered mechanism for an autoimmune response is posttranslational modification (PTM), resulting in the creation of a neoantigen that is recognized as nonself by the immune system. [21][22][23][24][25][26] A large percentage of proteins in the body are targets of PTM, and it is now clear that some of these modifications create new antigens that stimulate an autoimmune response. [21][22][23][24][25][26] One of the best-studied autoimmune diseases associated with PTM is celiac disease, a condition affecting %1% of the population of developed countries.…”

“…[21][22][23][24][25][26] A large percentage of proteins in the body are targets of PTM, and it is now clear that some of these modifications create new antigens that stimulate an autoimmune response. [21][22][23][24][25][26] One of the best-studied autoimmune diseases associated with PTM is celiac disease, a condition affecting %1% of the population of developed countries. 27 Celiac disease is a chronic small bowel disorder caused by an abnormal immune response to a tissue transglutaminase (TG2)-modified dietary protein, termed gliadin (a component of glutens that are prominent in wheat).…”

Immunoproteomics technologies in the discovery of autoantigens in autoimmune diseases

“…This approach is highly sensitive given the use of DNA-detection, rather than proteindetection methods (since the latter are limited by protein abundance). However, a crucial limitation of SEREX is that this method lacks the ability to differentiate or detect post-translational modifications (PTMs) that are likely to play a significant role in breaching immune tolerance in autoimmune diseases such as RA (65).…”