Monday, June 4, 2012

Error in immune system makes death much more likely

Analysis has revealed that a slight error in the immune system significantly increases the chance to die from a wide variety of diseases. Puzzling enough, what exactly causes the increase in mortality is unknown, but the error results in an increase in the concentration of a molecule known as a free light chain, which is part of the immune system's weapon arsenal. It is peculiar that such a seemingly innocent rise in the concentration of this particular molecule can cause such pronounced health effects.

Free light chain
The immune system protects our body from intruders and clears away old or malfunctioning cells. One of the tools it has at its disposal, is the antibody, a molecule that highly selectively binds to a foreign molecule, after which it is basically targeted for destruction. Antibodies consist of heavy chains and light chains, meaning that a free light chain is part of an antibody, but instead roams the blood on its own. Heavy and light chains are produced separately after which the antibody is assembled, but it was already known that most people produce a little extra light chains.
The structure of an antibody, where the light chain is green-coloured, and the heavy chain is blue-coloured. The heavy part also forms the base, or invariable part, of the antibody (number 4). Antibodies bind to their target by using the variable ends at the tips of the heavy and light chains (number 5).
At the Mayo Clinic, researchers set out to find correlations between concentration of free light chains in the blood, and survival rate. For their analysis, they picked data from a study carried out on approximately 16.000 people with a so-called plasma cell disorder; these cells are responsible for producing antibodies, which means a disorder would make them more likely to produce freely roaming light chains, or at least increase variability in production. After looking at the statistics, the scientists observed that the top 10 percent of light chain producers were four times more likely to die during the follow-up time of the study. Even after excluding possible confounders such as age, gender and kidney function, a high level of light chains was still found to be increasing the chance of death by two-fold.

Higher levels of free light chains cause people, on average, to die earlier due to a wide variety of illnesses, such as diabetes, cancer, cardiovascular diseases or even respiratory diseases. It is however unknown why the concentration of these molecules relates to a rather general increase in chance of death. Free light chain levels are possibly a biomarker for an underlying process, but this has so far not been elucidated. More research is required to find out what this really means, but it does seem a rather important finding if an increase in concentration of these molecules can have such profound health effects.

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