Persistence of elevated levels of galactosyl-alpha(1-3)galactose antibodies in sera from patients cured of visceral leishmaniasis

Abstract

Using rabbit erythrocyte-derived neutral glycosphingolipids enriched for a ceramide pentasaccharide as the antigen, we detected elevated anti-galactosyl-alpha(1-3)galactose (anti-G alpha G) antibody levels in 76% of children with active visceral leishmaniasis (kala-azar [KA]) and in 42% of clinically cured patients with KA who had been treated about 5 years previously with meglumine antimonate (30 mg/kg in a series of 15 daily injections). The long-term persistence of elevated G alpha G antibodies was also found in 56% of children living in the same geographic zone who, at the time of the initial clinical examination, had fever and evident splenomegaly with hyperglobulinemia but a negative bone marrow aspirate for leishmanial bodies. Five years after antimonate treatment, these clinically cured children with presumptive KA were studied serologically. Their mean G alpha G antibody values were slightly lower than those in patients with active KA but were still abnormal. Using different biochemical and immunological approaches, we found that elevated G alpha G antibodies present in patients with KA bound specifically to glycoconjugates with an alpha(1-3)-terminal galactose residue. G alpha G antibodies were mainly distributed between immunoglobulin classes G and M in patients with active KA and in antimonate-treated patients with clinically cured KA. The possibility of the existence of remnant living parasites or the persistence of inserted G alpha G epitopes in parasitized macrophages was proposed as a mechanism to explain the long-term persistence of abnormal G alpha G antibodies in patients apparently cured of KA.