CD55.

...

The function of CD55 is to provide a protective barrier threshold against complement activation

and deposition on the plasma membranes of normal autologous cells, especially by the

classical pathway, by limiting the formation and reducing the half-life of the C3 convertases. It is

widely expressed on cells throughout the body but its density of expression differs from one cell

type to other. Its weak expression on NK cells seems to be associated with reduced efficiency

of target cell lysis [17]. The molecular mass of CD55 on red blood cells is about 5kDa less than

Ruiz-Argüelles A and Llorente L, Page 4

on nucleated cells as a result of differential glycosylation. Genetic defects in the CD55 gene or

GPI-anchor attachment cause reduction or loss of CD55 (and CD59) on erythrocytes, and thus

the signs and symptoms of a rather uncommon disease called paroxysmal nocturnal

hemoglobinuria (PNH) [18,19].

Also called MIRL or protectin, CD59 is a single chain, GPI-anchored cell surface protein

structurally homologous to snake venom neurotoxins [26, 27], which is broadly expressed on

cells from all tissues. Its ex

The function of CD55 is to provide a protective barrier threshold against complement activation and deposition on the plasma membranes of normal autologous cells, especially by the classical pathway, by limiting the formation and reducing the half-life of the C3 convertases. It is widely expressed on cells throughout the body but its density of expression differs from one cell type to other.

Similarly to CD55, CD59 is incorporated in HIV envelope and protects virus and HIV infected cells against complement destruction. Also, CD59 transgenic mice, rats and pigs have been matter of study for xenotransplantation.

Paroxysmal nocturnal hemoglobinuria, the original link between complement regulators and human disease.

clinical manifestation of red cell lysis and release of hemoglobin into the urine that is manifested most prominently by dark-colored urine in the morning. The term "nocturnal" refers to the belief that the hemolytic episode was triggered by acidosis during sleep and activates complement to hemolyse an abnormally susceptible red cell membrane. However, this last observation has been disproved with time, and nowadays it is known that hemolysis is shown to occur throughout the day and is not even paroxysmal, but the overnight concentration of urine produces the dramatic change in color.

Because of the variety of symptoms observed during the initial manifestation and course of the disease, this condition has been referred to as the great impersonator.

The syndrome can present in 3 categories of clinical manifestations:

- an acquired intracorpuscular hemolytic anemia due to the increased susceptibility of the erythrocyte membrane to the lytic activity of complement.

- thromboses in large vessels, such as hepatic, abdominal, cerebral, and subdermal veins; and

- a mild to severe bone marrow hypoplasia that results in different degrees of pancytopenia.

Acquired deficiency of CD55 and CD59 in autoimmune hemocytopenias

The diminished expression of CD59 by erythrocytes in these patients might be due either to the impaired synthesis of the GPI anchor, or to the abnormal coupling of the protein to the membrane cohering by the reticulocytes or red blood cell precursors. Another, although rather feeble explanation could be an augmented cleavage of CD59 from the red cell surface by enzymes such as the phosphatidylinositol-specific phospholipase C, or D, for this would be specific for phosphatidylinositol while not only for CD59.

Autoimmune Thrombocytopenia

Thirty patients diagnosed as ATP by clinical and laboratory criteria were studied and their results were compared with 30 sex and age matched healthy individuals. Deficient expression of CD59 was more common than that of CD55 in patients, as compared to controls (36 versus 16%). Moreover, CD59 deficiency was associated to the severity of thrombocytopenia, whilst CD55 deficiency was not. Deficiency of CD55, CD59, or both, was not associated to the presence of detectable platelet-reactive antibodies in the patient’s sera. Selected experiments were performed in samples from patients that showed diminished expression of CD55 or CD59 in their platelets, to asses if platelet age was related to these deficiencies. We found that large reticulated (young) platelets always expressed normal amounts of CD55 and CD59, while deficiency in the expression of these proteins was restricted to mature platelets

Systemic Lupus Lymphopenia

Both T and B cells from lymphopenic SLE patients showed a decreased expression of CD55 and CD59 as compared with cells from healthy individuals, whereas lymphocytes from non-lymphopenic lupus patients were found to have increased expression of both molecules when compared to controls. These differences were unrelated to disease activity or therapy for both treatment regimes and activity were similar in lymphopenic and non-lymphopenic patients. Overexpression of complement regulators has been previously found in other cells and tissues, such as the increased density of CD55 and CD59 in the renal glomeruli affected by diffuse proliferative glomerulonephritis, in the salivary glands of patients with Sjögren’s syndrome and in endothelial cells exposed to molecules with pro-inflammatory activity.

Concluding remarks

We initiated this series of studies, we hypothesized that autoantibodies, most likely those bearing reactivity towards phospholipids, could be responsible for the decreased expression of complement regulatory proteins CD55 and CD59. Antibodies with phospholipid reactivity might hinder the binding of the proteins to the GPI anchorage, or shed the GPI-protein complexes from the cell surface of erythrocytes, platelets and lymphocytes. In the case of lymphocytes, internalization