Abstract
Pathogenesis in kala-azar is associated with depressed cellular
immunity and significant elevation of antileishmanial antibodies. Since
these antibodies are present even after cure, analysis of the
parasite-specific isotypes and immunoglobulin G (IgG) subclasses in
kala-azar patients may shed new light on the immune responses during
progression and resolution of infection. Using leishmanial membrane
antigenic extracts, we investigated the relative levels of specific
IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera
during disease, drug resistance, and cure. Acute-phase sera showed
strong stimulation of IgG, followed by IgE and IgM and lastly by IgA
antibodies. IgG subclass analysis revealed expression of all of the
subclasses, with a predominance of IgG1 during disease. Following
sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE,
and IgG4 remained constant, while there was a decrease in the titers of
IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1
was observed in these individuals. Cure, in both SAG-responsive and
unresponsive patients, correlated with a decline in the levels of IgG,
IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and
the persistence, most importantly, of IgE and IgG4 following drug
resistance, along with a decline in IgE, IgG4, and IgG1 with cure,
demonstrate the potential of these isotypes as possible markers for
monitoring effective treatment in kala-azar.