Autoimmunity & protein modification

Posted on : 26-06-2011 | By : Fabio Sanchez | In : Articles

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Our experience of the world is possible because of innumerable bits of information speeding through our senses but at a more essential level our very being is possible because of innumerable messages coded in our DNA and in our environments. Our genes code for precise messages, that reach their destination after being modified by different metabolic processes. The central theorem of genetics says that DNA contains the code necessary to produce all the proteins in an organism. Those coded messages, that we call genes, get transcribed into RNA and after translated into proteins by specialized molecular machines. This view is accurate but not quite complete. Proteins in their final forms are not exact reflections of their original DNA code. During their production they suffer modifications that are not coded into their original DNA, although some sequences -hidden messages – inside the proteins influence how their own chemical modifications are carried out by other molecules we call enzymes. Thus, the original appearance of a protein after being produced is short lived. Protein surfaces get folded onto each other giving each protein a characteristic three dimensional appearance. After, proteins often get linked to other proteins or to other types of chemicals that modify protein structure and function. For example sugars are added in a process called glycosylation,  methyl groups are added in a process called methylation and so on and so forth. thus, methylation of histones, the proteins that help DNA maintain their structure inside cells, is responsible for silencing certain genes during embryonic development. Likewise, addition of diverse types of sugars or other chemical groups to proteins is very important for the proper functioning of our bodies. But sometimes, such chemical changes on our proteins, occur because of foreign substances that enter our bodies, for example, infections or chemical pollutants. One such situation seems to happen in some patients with rheumatoid arthritis (RA) who have the habit of smoking. It appears that people with certain genetic predisposition change the appearance of their normal cartilage proteins through smoking. Their own immune systems stop recognizing such proteins as part of the body which causes an autoimmune reaction, or self inflicted damage. The chemical change is called citrullination and the self inflicted damage becomes what we know as rheumatoid arthritis. Citrullination is not the only change that happens in RA but it is an important contributing factor.
It is possible that specific autoimmune diseases have each specific chemical changes to specific types of proteins, which could explain why chronic inflammatory diseases have different clinical manifestations.
It is therefore important to recognize the people who are likely to respond in such a negative way to smoking and possibly other forms of chemical pollution by studying their genetic profiles. Citrullination in relation to RA is discussed in detail in the following link:
Semin Immunol. 2011 Apr;23(2):92-8. Epub 2011 Mar 3.

Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis.