Evolution,Apoptosis,and Autoimmune Diseases

Abstract

Apoptosis is a physiological means of cell elimination. The process is encoded in the chromosome of cells and is activated only in cells destined to die. Such cells are not wanted due to various physiological situations. They include cells in the web tissue between our fingers during embryonic development, and lymphocytes that react against self during maturation in the thymus. In the apoptotic cells, the organelles are condensed, the chromatids are cleaved into 180-200 kb bases, and wrapped by cell membranes into apoptotic bodies. The apoptotic bodies contain intracellular components that can cause immunologic diseases, most noticeable is the mitochondrial DNA, which is bacterial in origin, and can cause marked autoantibody formation. If an organism shows defective apoptosis, the cellular contents that should have been wrapped up in the apoptotic bodies, now with defective apoptosis, would leak into the circulation, and causes autoimmune disease in two strains of mice, the lpr/gld mice. Introduction of a normal apoptotic gene into one of the mice has greatly corrected the manifestation of autoimmune disease, including systemic lupus erythematosus (SLE), glomerulonephritis, and lymphadenopathy. A human counterpart of the autoimmune lymphoproliferative syndromes exists that mimics the lpr/gld murine model. In nature, such mice may not be the fittest, especially if arthritis is part of the autoimmune disease manifestation. From Darwin's Survival of the Fittest, these mice will not survive. Thus, evolution chooses apoptosis as a means of physiological cell elimination as opposed to necrosis.