Australian scientists have shed new light into how some autoimmune diseases can take hold, identifying the exact conditions under which an infection can prompt the body to attack itself.
The medical community has long understood that autoimmune diseases such as rheumatic fever, wherein the body creates antibodies that attack the heart, can develop after the body tries to fight off infections.
But little was known about how these kinds of infection-driven autoimmunity occurred or why the body was unable to prevent them.
Tyani Chan and Robert Brink from Sydney's Garvan Institute of Medical Research studied mice to investigate what could prompt an infection-driven autoimmune attack.
They were focused on the antibody-creating B cells that play a crucial role in the body's response to disease.
When the body is fending off an infection, B cells can mutate their antibody genes randomly until they produce one that 'sticks' to the invading antigen.
This process occurs within specialised environments in the lymph system known as 'germinal centres'.
Dr Chan and Associate Professor Brink demonstrated that when antigen is abundant and available throughout the body, rogue autoantibody-generating B cells are deleted and autoimmunity avoided.
But when target antigen is located only in a tissue or organ remote from the germinal centre, B cells capable of reacting against both antigen and 'self' are able to escape the germinal centre and produce autoantibodies.
"Essentially we've shown there's a big hole in self-tolerance when it comes to cross-reactive autoantibodies that can attack organ-specific targets," Associate Prof Brink said in a statement.
"Our finding explains a lot about how autoimmune conditions that target particular organs such as the heart or nervous system could develop after an infection.
"It also suggests that if you know enough about the disease and the molecular messaging systems involved, it may be possible in future to modulate the germinal centre response."
The findings were published in the international journal, Immunity, on Friday.