Aplastic anemia Aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… and Paroxysmal Nocturnal Hemoglobinuria Hemoglobinuria: (hee-muh-gloe-buh-NYOOR-ee-uh) The presence of hemoglobin in the urine. (PNH) are two serious blood disorders that share one important feature: the bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. cannot always keep up with the body’s needs for blood cells. We call this feature bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… (BMF); it means that there may be anemia anemia: (uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness. , low white cells (particularly neutropenia neutropenia: (noo-truh-PEE-nee-uh) A condition in which there is a shortage of neutrophils in the bloodstream. Neutrophils are a type of white blood cell. This results in a low white blood cell count. , entailing the risk of infection), low platelets (with risk of bleeding). Recently we have analyzed in depth a type of lymphocyte lymphocyte: A type of white blood cell. B lymphoctyes, or B cells, help make special proteins called antibodies that fight bacteria and viruses (immune response). T lymphocytes, or T cells, help kill tumor cells and help the body's immune response. cells called T cells in patients with PNH, and we have found that they have an excess of a very rare subset of T cells that are able to recognize a specific glycolipid molecule (a molecule that contains both a sugar moiety and a fat moiety) – we have called them GPI-reactive T cells. We now plan to investigate whether GPI-reactive T cells are also increased in aplastic anemia. Our findings would corroborate the notion that these cells are prime movers of the disease and therefore may make it possible to develop new forms of treatment.
In the first year of this project we have started to investigate the presence of CD1d restricted GPI-reactive T cells in
aplastic anemia
aplastic anemia:
(ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most…
. We have found that GPI-reactive cells were present in 8 out of 10 aplastic anemia patients, but in follow-up with these patients there was a lower frequency of those cells. It is possible that the frequency of the GPI-reactive T cells, which are likely responsible for the auto-immune attack to the normal (GPI+)
hematopoiesis
hematopoiesis:
(hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow.
, is affected by the immunosuppressive treatments. We will test this possibility by studying the samples from the patients we have already studied at diagnosis.
Our starting hypothesis was that GPI-reactive T cells should more likely be present in aplastic anemia patients with a substantial proportion of GPI-negative (PNH) blood cells. Thus is was unexpected and very interesting that we found a high frequency of GPI-reactive T cells in all aplastic anemia patients without detectable PNH blood cells. This preliminary observation, if confirmed in a larger number of such aplastic anemia patients, suggests that the GPI-reactive T cells are implicated in the pathogenesis of most cases of both aplastic anemia and PNH. These findings support the view that there is more than a close link between aplastic anemia and PNH; in fact they suggest that in most cases aplastic anemia and PNH are just different clinical presentations of the same disease. In both aplastic anemia and PNH, GPI-reactive T cells could be responsible for the auto-immune attack targeting the GPI+ hematopoiesis, thus the emergence of GPI-negative clones depends only on the “degree” of staminality of pre-existent PIG-A mutated hematopoietic
stem cells
stem cells:
Cells in the body that develop into other cells. There are two main sources of stem cells. Embryonic stem cells come from human embryos and are used in medical research. Adult stem cells in the body repair and maintain the organ or tissue in which they are found. Blood-forming (hemapoietic) stem…
.
In the second year of this project we will study the possible variation of the frequency of GPI-reactive T cells upon immunosuppressive treatments during the follow-up with the patients we have already studied at diagnosis. In addition, we are collecting samples from a new series of aplastic anemia patients at diagnosis and during their follow-up.
Aplastic anemia
Aplastic anemia:
(ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most…
(AA) and
Paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria:
(par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A…
(PNH) are two blood disorders that share one important feature called
bone marrow failure
bone marrow failure:
A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be…
: the
bone marrow
bone marrow:
The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow.
cannot keep up with the body’s needs for blood cells. It means that there may be
anemia
anemia:
(uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness.
, low white cells (entailing the risk of infection), low platelets (with risk of bleeding).
Recently we have studied a type of lymphocytes called T cells in patients with PNH, and we have found that they have an excess of a very rare subset of T cells that are able to recognize a specific glycolipid molecule (GPI): we have called these lymphocytes “GPI-‐reactive T cells”. The GPI-‐reactive T cells could be responsible for the bone marrow failure because they should be able to attack/destroy the normal blood marrow cells that display on their surface the GPI molecules.
The aim of this project was to investigate whether GPI-‐reactive T cells are also increased in AA. During the two years of this project, studying a large number of patients (both AA and PNH) and healthy controls, we have found that GPI-‐reactive T cells, detected with different techniques, are present and increased in the large majority (more than 70%) of patients with AA. These findings corroborate the notion that AA and PNH are two side of the same disease and that GPI-‐reactive T cells could be the prime responsible for the bone marrow failure typical of these disease. In this respect, a very intriguing observation is that the number of these GPI-‐ reactive T cells is reduced by the immunosuppression that is used to treat most of AA patients.