The potential for induction of autoimmune disease by a randomly-mutated self-antigen.

TY - JOUR

T1 - The potential for induction of autoimmune disease by a randomly-mutated self-antigen.

AU - Pedersen, Anders Elm

N1 - Keywords: Autoantigens; Autoimmune Diseases; Humans; Models, Genetic; Models, Immunological; Mutation; Transcription, Genetic

PY - 2007

Y1 - 2007

N2 - The pathology of most autoimmune diseases is well described. However, the exact event that triggers the onset of the inflammatory cascade leading to disease is less certain and most autoimmune diseases are complex idiopathic diseases with no single gene known to be causative. In many cases, a relation to an infectious disease is described, and it is thought that microbes can play a direct role in induction of autoimmunity, for instance by molecular mimicry or bystander activation of autoreactive T cells. In contrast, less attention has been given to the possibility that modified self-antigens can be immunogenic and lead to autoimmunity against wildtype self-antigens. In theory, modified self-antigens can arise by random errors and mutations during protein synthesis and would be recognized as foreign antigens by naïve B and T lymphocytes. Here, it is postulated that the initial auto-antigen is not a germline self-antigen, but rather a mutated self-antigen. This mutated self-antigen might interfere with peripheral tolerance if presented to the immune system during an infection. The infection lead to bystander activation of naïve T and B cells with specificity for mutated self-antigen and this can lead to epitopespreading in which T and B cells with specificity for wildtype self-antigens are activated as a result of general inflammation.

AB - The pathology of most autoimmune diseases is well described. However, the exact event that triggers the onset of the inflammatory cascade leading to disease is less certain and most autoimmune diseases are complex idiopathic diseases with no single gene known to be causative. In many cases, a relation to an infectious disease is described, and it is thought that microbes can play a direct role in induction of autoimmunity, for instance by molecular mimicry or bystander activation of autoreactive T cells. In contrast, less attention has been given to the possibility that modified self-antigens can be immunogenic and lead to autoimmunity against wildtype self-antigens. In theory, modified self-antigens can arise by random errors and mutations during protein synthesis and would be recognized as foreign antigens by naïve B and T lymphocytes. Here, it is postulated that the initial auto-antigen is not a germline self-antigen, but rather a mutated self-antigen. This mutated self-antigen might interfere with peripheral tolerance if presented to the immune system during an infection. The infection lead to bystander activation of naïve T and B cells with specificity for mutated self-antigen and this can lead to epitopespreading in which T and B cells with specificity for wildtype self-antigens are activated as a result of general inflammation.

U2 - 10.1016/j.mehy.2006.10.054

DO - 10.1016/j.mehy.2006.10.054

M3 - Journal article

C2 - 17197112

SN - 0306-9877

VL - 68

SP - 1240

EP - 1246

JO - Medical Hypotheses

JF - Medical Hypotheses

IS - 6

ER -