Variable degree of alternative complement pathway–mediated Hemolysis in Indian Visceral Leishmaniasis induced by differential expression of 9‐O–acetylated sialoglycans

Abstract

Background: Increased expression of linkage-specific 9-O-acetylated sialoglycans (9-O-AcSGs) has been demonstrated on erythrocytes from patients with visceral leishmaniasis (VL) by use of Achatinin-H. We assessed the capacity of this glycotope to influence hemolysis via activation of the alternative complement pathway in patients with VL, compared with that in healthy control subjects. Methods: The differential expression of 9-O-AcSGs on surfaces of erythrocytes was measured, 9-O-AcSGs were affinity purified, and the molecular determinants were identified byWestern blotting. The degree of alternative complement pathway-mediated hemolysis was compared with expression of 9-O-AcSGs on erythrocytes. Results: Enhanced expression of linkage-specific 9-O-AcSGs was demonstrated on erythrocytes from patients with active VL. Six distinct molecular determinants present only on diseased erythrocytes were affinity purified and were absent after elimination of parasite burden. A correlation (r²=0.9) was observed between the presence of 9-O-AcSGs and the degree of alternative complement pathway-mediated hemolysis. Conclusion: The 9-O-AcSGs expressed on erythrocytes from patients with VL are potent complement activators, causing enhanced hemolysis via activation of the alternative complement pathway, and may account for the anemia that is a common manifestation of VL.