Note: This review is based upon a presentation at the 2012 American Society of Hematology (ASH) Annual Meeting, December 7-10 in Atlanta, Georgia.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report.
Abstract Number #647
Lucia Gargiulo, Michela Sica, Maria Papaioannou, Giulia Talini, Aristeidis Chaidos, Barbara Richichi, Andrei V Nikolaev, Cristina Nativi, Mark Layton, Josu de la Fuente, Irene Roberts, Lucio Luzzatto, Rosario Notaro, and Anastasios Karadimitris
Aplastic anemia is a disease where the patients’ immune system attacks his or her own bone marrow. Normally, such an attack should be reserved for the killing of harmful microbes. This type of mis-directed immune reaction is called auto-immunity. In fact, there are many different types of auto-immune diseases. In some cases it is known what molecule (usually a protein) the immune system is mistakenly recognizing as a foreign microbe. However, we do not yet know for sure what this molecule is in aplastic anemia. At first glance, PNH seems to be a different type of disease. Here the PNH cell is not attacked because of a molecule it has, but rather, because of something it does not have. In PNH there is a lack of certain proteins on the surface of the red blood cells. These proteins (such as CD55 and CD59) normally prevent the red cell from being broken down by complement proteins. In a way, PNH could also be thought of as an auto-immune disease, since complement proteins are a part of the immune system.
For a long time it has been believed that PNH should be considered an autoimmune disease for a different reason—because it occurs commonly in patients who have had aplastic anemia. Here the authors have done a study looking at blood cells from patients with PNH and they provide experimental evidence for why PNH should be thought of as an autoimmune disease. At the same time, they have given us a hint of the molecule that the immune system is mistakenly seeing as belonging to a foreign microbe in at least some patients with aplastic anemia. They show that patients with PNH have immune cells that are primed to attack other cells that have the molecule GPI—which is a structure associated with proteins such as CD55 and CD59 on normal cells. This can be taken as evidence to support the immune escape model of PNH. In this model, normal individuals all have rare cells that are missing CD55 and CD59-- and in fact, you can see a few PNH cells in normal individuals if you look at over 1 million cells. However, healthy individuals will not then go on to develop PNH because these rare PNH cells do not have any advantage in a normal situation. However, in some people, aplastic anemia develops and stem cells are injured as a result of the immune system mistakenly recognizing marrow cells as being foreign. If it is GPI that the immune system recognizes as foreign, then these rare PNH cells will now thrive in this environment, because they are missing GPI. Eventually, the PNH cells expand so that now instead of being rare, they make up a large proportion of the patients’ blood cells. If the PNH cells expand quickly enough, the patient may never know that they had actually had aplastic anemia before developing PNH. If the PNH cells are slow in expanding, then the patient may experience aplastic anemia first and then later experience PNH.