Persistence of elevated levels of galactosyl-α(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-α(1-3)galactose (anti-GαG) 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 GαG 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 GαG 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 GαG antibodies present in patients with KA bound specifically to glycoconjugates with an α(1-3)-terminal galactose residue. GαG 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 GαG epitopes in parasitized macrophages was proposed as a mechanism to explain the long-term persistence of abnormal GαG antibodies in patients apparently cured of KA.