Study On The Effects Of Iymphocytes In The Pathogenesis Of Paroxysmal Nocturnal Hemoglobinuria

BACKGROUND:Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by intravascular hemolysis, episodes of hemoglobinuria and life threatening venous thrombosis. A number of proteins are missing from the membrane of the abnormal blood cells found in PNH, including the molecules which regulate the activation of complements (CD55 and CD59), that cause the hemolysis. All of these cell-surface proteins have a common structural feature of being anchored to the cell surface by a glycosylphosphatidylinositol (GPI) moiety which is deficient in PNH clone. A gene, PIG-A required for the biosynthesis of GPI moiety, is somatically mutated in PNH patients. However, it is not clear what has caused the defective PNH clone to proliferate preferentially in the hematopoisis of PNH patients. Because there is a close relationship between PNH and aplastic anemia, many researchers infered that PNH clone could escape from T lymphocytes' injury and acquire surviving advantages. Is the function of T lymphocytes abnormal in PNH patients? Do T lymphocytes have different effects on PNH clone and normal clone? There are a few reports on the study of T lymphocytes' function, but the results are controversial. Furthermore, there is no report on the effect of T lymphocytes in the pathogenesis of PNH.Treatment of PNH is generally palliative, including suppressing hemolysis, red cells transfusion, iron replacement and folic acid supplement. Adrenocortical hormone has been proven useful for suppressing hemolysis in more than half of PNH patients, and is still the main drug for PNH up to now. But it's mechanism is not clear. Some PNH patients had no response to adrenocortical hormone or they were dependent on it. It is difficult to cure these refractory and relapsed cases. Since 1960s, some researchers have found that heparin could suppress the hemolysis of red cells from PNH patients in vitro through inhibiting complement 3 (C3) binding to red cells. However, the concentration of heparin suppressing the hemolysis in vitro could result in a risk of hemorrhages in vivo, and could not be tolerated by most of PNH patients. Low-molecular weight heparin (LMWH) has the similar effects as heparin, but seldom causes hemorrhages, which indicates that LMWH may be clinically useful for suppressing the hemolysis in vivo of patients with PNH.OBJECTIVES:1. To study the T lymphocytes' function by examing the activated phenotype of T lymphocytes, the negative cytokines secreted by T lymphocytes and the capacity of proliferation and anti-tumor of T lymphocytes.