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  • 1
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 43, No. 3 ( 2005-03), p. 1269-1277
    Abstract: Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), caused by Leishmania donovani , is difficult, as the dermal lesions are of several types and resemble those caused by other skin diseases, especially leprosy. Since the disease generally appears very late after the clinical cure of kala-azar in India, it is also difficult to correlate PKDL with a previous exposure to L. donovani . Very few attempts have been made so far to diagnose PKDL serologically, and the diagnostic methods vary in their sensitivities and specificities. Diagnosis of PKDL through sophisticated PCR methods, although highly sensitive, has limited practical use. We have developed a serodiagnostic method using an enzyme-linked immunosorbent assay to detect specific immunoglobulin (Ig) isotypes and IgG subclass antibodies in the sera of Indian PKDL patients. Our assay, which uses L. donovani promastigote membrane antigens, was 100% sensitive for the detection of IgG and 96.7% specific for the detection of IgG and IgG1. Optical density values for individual patients, however, demonstrated wide variations. Western blot analysis based on IgG reactivity could differentiate patients with PKDL from control subjects, which included patients with leprosy, patients from areas where kala-azar is endemic, and healthy subjects, by the detection of polypeptides of 67, 72, and 120 kDa. The recognition patterns of the majority of serum samples from patients with PKDL were also distinct from those of the serum samples from patients with visceral leishmaniasis (VL), at least for a 31-kDa polypeptide. To further differentiate patients with PKDL from those with active and cured VL, we analyzed the specific titers of the Ig isotypes and IgG subclasses. High levels of IgG, IgG1, IgG2, and IgG3 antibodies significantly differentiated patients with PKDL from patients cured of VL. The absence of antileishmanial IgE and IgG4 in patients with PKDL differentiated these patients from those with active VL. These results imply intrinsic differences in the antibodies generated in the sera from patients with PKDL and VL.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2005
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 2
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 179, No. 8 ( 2007-10-15), p. 5592-5603
    Abstract: Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-γ and IL-12. We address the role of the differential decline of IL-10 and TGF-β in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-β in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-γ and IL-12 production, and elevation of IL-10 and TGF-β. Cure corresponded with an elevation in IFN-γ and IL-12 production and down-regulation of IL-10 and TGF-β. Both CD4+ and CD8+ T cells were involved in IFN-γ and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-β in some SAG-treated individuals and the elevation of IL-10 and TGF-β in PKDL, a sequel to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB treatment of VL resulted in negligible TGF-β levels and absolute elimination of IL-10, reflecting the better therapeutic activity of AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-β, IL-10, and Ab production. In addition, the enhancement of CD4+CD25+ T cells in active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease forms.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2007
    detail.hit.zdb_id: 1475085-5
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