A 17-year-old boy is taken to the emergency department because of severe abdominal and lumbar pain.Physical examination reveals splenomegaly,and laboratory studies reveal hemoglobinemia and thrombocytopenia.A urine sample is remarkable for gross hemoglobinuria.The patient reports a history of bloody urine on multiple occasions in the past.Flow cytometric analysis of the patient's red blood cells (RBC)will most likely indicate reduced or absent expression of which pair of molecules that is normally present on RBC membranes?

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The patient's history is consistent with a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH;Marchiafava-Micheli syndrome),which is due to a genetic defect in the synthesis of glycosyl-phosphatidyl-inositol (GPI)anchors for membrane proteins.Two important regulatory proteins of the complement system,DAF (CD55)and CD59,are expressed as GPI-linked membrane proteins,and therefore their expression is reduced in PNH.DAF normally promotes dissociation of C3 convertase that spontaneously forms on blood cells at a low level.CD59 prevents assembly of poly-C9 and MAC-mediated lysis of blood cells.Without sufficient expression of CD55 and CD59,red blood cells and platelets are susceptible to complement-mediated membrane damage,causing thrombosis and hemolysis.CR1 and CR2 deficiencies have not been reported.C1 INH deficiency causes hereditary angioneurotic edema.C4bp and factor H are not membrane proteins,but rather are soluble plasma proteins that block classical and alternative C3 convertase formation,respectively.CR3 and CR4 are integrins that function as adhesion molecules on leukocytes as well as on complement receptors.Leukocyte adhesion deficiency I,caused by mutations in the gene encoding the CD18 F1F1F1S1F1F1F10 chain of these integrins,manifests as an immunodeficiency disease.

A 17-Year-Old Boy Is Taken to the Emergency Department Because