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.