[Greg H]

Marmab,

Warning! Greg is about to try to be helpful by talking about something they hadn't even invented when he was in college and that therefore he has learned about but never been tested on (not to mention he was a religion major and thus hasn't seen a cell under a microscope since 9th grade)! Please jump in a correct me if I type something stupid.

The CD-system is a way of classifying different kinds of blood cells. As I understand it, it's based on protein (or glycoproteins) found on the surface of the cells.

The CD4 and CD8 cells are both T cells, a kind of lymphocyte, which is a kind of white blood cell. The CD8 cells are real killers; they actually go after bad cells (like some viral infection you pick up from your favorite niece), attack them, and kill them. The CD4s are more helpers or pointers. They hold up a sign that says, "Danger, Will Robinson! Incoming nasty cells. Please come kill them!" And that gets the CD8s all excited to go kill things. [BTW, I am not trying to over-simplify this; this is the over-simplified way I understand it myself.]

The CD4s and CD8s are kind of like Special Forces units in the US military, which are often specialized on a specific country, learning the language spoken there, the customs, etc. So, if you pick up some virus for the first time, let's call it the "nastystuffinmyspinachmakesmehurl" virus, or NSMSMH, some CD4s and CD8s will start to specialize in that virus, and, even after they have killed it, you'll have a nice little bunch of experts on NSMSMH hanging out in your immune system just waiting for it to crop up again and very good at killing it.

So . . . . in the world of immune-related MDS, what we think is happening is that some of these CD4 and CD8 T cells have become specialized in attacking your very own bone marrow stem cells (which, by the way, have their very own CD numbers).

The late Dr. Elaine Sloand, at NIH, wanting to prove this, picked one specific type of abnormal stem cell -- those with Trisomy 8 -- and demonstrated that, in fact, folks with Trisomy 8 have a special little CD4/CD8 unit that attacks Trisomy 8 stem cells. When this attack happens, it releases a lot of seriously nasty chemicals called "cytokines" in the marrow, and, Sloand believed, those cytokines both suppress blood production and cause additional chromosomal damage over time. And, though they picked the Trisomy 8 to study, the folks at NIH believe that other chromosomal abnormalities also inspire their own little squads of killer CD4/CD8s.

The idea behind immunosuppression for MDS is to kill off these squads, stop the attacks on your stem cells, and hope that the ceasefire will allow the marrow to heal. Unfortunately, the drugs that do that, ATG, Cyclosporine, and Campath, aren't specific for the CD4/CD8 squads, but knock out a whole bunch of other white blood cells, too, making you susceptible to various infections. So, you have to take prophylactic antibiotics for a while when you've done immunosuppressive therapy.

Now, after that big long explanation, I have to admit that I do not know the answer to your question about the significance of the CD4/CD8 inversion in AA, so we'll have to hope Lisa jumps in and explains that to us both.

Hope that helps . . .

Greg