<prompt> CD59 defect is seen as marker of which diseaseParoxysmal Nocturnal HemoglobinuriaPTENHereditary spherocytosisCowden syndrome  <response>: A Paroxysmal Nocturnal Hemoglobinuria PNH?PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PNH is a disease, due to acquired mutations in Phosphatidyl Inositol Glycan Complementation Group gene PIGA..oAssociated with deficiency of glycosylphosphatidylinositol GPI anchor proteins along with absence of external surface membrane proteins attaching to it.oCD55 DAF and CD59 MIRL are two such complement defence proteinsoCD59 deficiency:oCommon finding in RBCs WBCs of patients with chronic hemolysis suffering from PNHoDiagnosis: Based on demonstration of a substantial proportion of patients RBC having increased susceptibility to complement C, due to the deficiency on their surface of proteins particularly CD59 CD55?Pathogenesis of CD55 CD59:oInherited absences of both proteins in humans have been described:-Most inherited deficiencies of CD55 - no district clinical hemolytic syndrome-Inherited absence of CD59 - produces a clinical disease similar to PNH with hemolysis recurrent thrombotic events?Paroxysmal nocturnal hemoglobinuria PNH:oCD59 inhibit C9 bind to C5b, 6,7,8oDecay-accelerating factor DAF displace Bb from C3b and C2b from C4boBoth CD59 DAF are defect in PNHSTAGES AT WHICH COMPLEMENT ACTIVITY IS REGULATEDC1q binding to antigen: antibody complexes activates C1r and C1sC1 inhibitor C1INH dissociates C1r and C1s from the active C1 complex.C4b,2b is the active C3 convertase cleaving C3 to C3a and C3bDAF, C4BP and CR1 displace C2b from the C4b, 2b complex. C4b bound by C4BP, MCP, or CR1 is cleaved by a soluble prolease I to inactive forms C4d and C4c.The C5 convertases cleave C5 to C5a and C5b.CR1 and H displace C3b. CR1 and H act as cofactors in the cleavage of C3b by I.The terminal components of complement form a membrane pore - the membrane attack complex.CD59 prevents final assembly of the membrane attack complex at the C8 to C9 stage.Other Options?PTEN phosphatase and tensin homologue-Is a membrane-associated phosphatase encoded by a gene on chromosome 10q23 that is mutated in Cowden syndrome, an autosomal dominant disorder marked by frequent benign growths, such as skin appendage tumors, and an increased incidence of epithelial cancers, particularly of the breast, endometrium, and thyroid.?Hereditary spherocytosis HS:-Is an inherited disorder caused by intrinsic defects in the red cell membrane skeleton that render red cells spheroid, less deformable vulnerable to splenic sequestration and destruction.-The prevalence of HS is highest in northern Europe, where rates of 1 in 5000 are reported.?Cowden syndrome:-Dysplastic gangliogliocytoma of the cerebellum Lher- mitte-Duclos disease, caused by mutations in PTEN resulting in PI3KAKT signaling pathway activity. 