O papel das proteínas reguladoras do complemento CD55/CD59 em células de sangue periférico de pacientes com lúpus eritematoso sistêmico

Abstract

CD55 and CD59 are glycosylphosphatidylinositol-anchored proteins with regulatory properties on the activating cascades of the complement system. This regulation occurs through inhibition of the C3-convertase formation by CD55, and prevention of the terminal polymerization of the membrane attack complex by CD59. Deficiency in the expression of these proteins can be associated with increased susceptibility to complement-mediated cell death. Systemic lupus erythematosus patients with hemolytic anemia and lymphopenia seem to have an acquired deficiency of CD55 and CD59 proteins. However, the mechanisms involved in this deficiency and its impact on the clinical manifestation of SLE needs to be further investigated.

Frequency of paroxysmal nocturnal hemoglobinuria in patients attended in Belém, Pará, Brazil

“…Despite of not having been one of the objectives of this work, it is important to comment that some hypotheses could explain the occurrence of the three inconclusive cases: the presence of small clonal populations of PNH cells masked by normal cells from transfusions within the three months prior to the tests; (5,7,11-13,16,17) small populations of granulocytes without glycosylphosphatidylinositol-anchored proteins in patients with aplastic anemia or myelodysplastic syndrome but without evidence of hemolysis or other presentations of PNH, with the exception of altered hematopoietic production, and cross reactions with auto-antibodies for other autoimmune diseases such as systemic lupus erythematosus, (3,9,10,12) as was observed in one of the inconclusive cases presented in this study and only diagnosed correctly as negative for PNH after the suspension of treatment with prednisone.…”

“…Rarely, spontaneous remission occurs (10% to 15% of cases) or transformation to acute myeloid leukemia. (3,9,13,14) …”

Frequency of paroxysmal nocturnal hemoglobinuria in patients attended in Belém, Pará, Brazil

“…Despite of not having been one of the objectives of this work, it is important to comment that some hypotheses could explain the occurrence of the three inconclusive cases: the presence of small clonal populations of PNH cells masked by normal cells from transfusions within the three months prior to the tests; (5,7,(11)(12)(13)16,17) small populations of granulocytes without glycosylphosphatidylinositolanchored proteins in patients with aplastic anemia or myelodysplastic syndrome but without evidence of hemolysis or other presentations of PNH, with the exception of altered hematopoietic production, and cross reactions with autoantibodies for other autoimmune diseases such as systemic lupus erythematosus, (3,9,10,12) as was observed in one of the inconclusive cases presented in this study and only diagnosed correctly as negative for PNH after the suspension of treatment with prednisone.…”

“…Point mutations can also occur producing a partially functional molecule. (3)(4)(5)(6) This defect results in a deficiency in the biosynthesis of glycosylphosphatidylinositol (GPI) which is responsible for the anchorage and fixation of the regulatory antigens of the complement system (CS), CD55 antigen or decay accelerating factor (DAF) and CD59 antigen or membrane inhibitor of reactive lysis (MIRL), on the outer surface of erythrocyte, leukocyte and platelet membranes. This makes these cells vulnerable to lysis mediated by complement which results in hemolytic anemia, a certain degree of bone marrow insufficiency and the release of large amounts of free hemoglobin into the plasma, which can lead to an increase in the consumption of nitric oxide and clinical manifestations that include fatigue, abdominal pain, esophageal spasms, erectile dysfunction and various degrees of thrombosis (classic or subclinical PNH).…”

“…Rarely, spontaneous remission occurs (10% to 15% of cases) or transformation to acute myeloid leukemia. (3,9,13,14) The diagnosis of PNH is based on clinical findings and laboratory tests that detect GPI-binding to red cell membrane proteins or that demonstrate the presence of red blood cells that are exceptionally sensitive to hemolysis by the complement system. These tests include the acidified serum test (Ham's test), determination of the CD55 and CD59 antigens using gel column technology or immunophenotyping by flow cytometry.…”