Immune response to Leishmania antigens in an AIDS patient with mucocutaneous leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome (IRIS): a case report

Abstract

Background: After the onset of HAART, some HIV-infected individuals under treatment present a exacerbated inflammation in response to a latent or a previously treated opportunistic pathogen termed immune reconstitution inflammatory syndrome (IRIS). Few reports of tegumentary leishmaniasis have been described in association with IRIS. Moreover, the immunopathogenesis of IRIS in association with Leishmania is unclear.

Case presentation: The present study reports on a 29-year-old HIV-infected individual who developed mucocutaneous leishmaniasis associated with immune reconstitution inflammatory syndrome (IRIS) five months following highly active antiretroviral therapy (HAART). Severe lesions resulted in the partial destruction of the nasal septum, with improvement observed 15 days after treatment with Amphotericin B and corticosteroids. The immune response of this patient was evaluated before and after the lesions healed. IRIS was diagnosed in association with high levels of TNF-α and IL-6. Decreased production of IFN-γ and a low IFN-γ/IL-10 ratio were also observed in response to Leishmania antigens. After receiving anti-leishmanial treatment, the individual's specific Th1 immune response was restored.

Conclusion: The results suggest that the production of inflammatory cytokines by unstimulated T-lymphocytes could contribute to occurrence of leishmaniasis associated with IRIS.

Figure 1

A time line of clinical manifestation of a patient with mucocutaneous leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome.

Figure 2

An HIV-infected patient with mucocutaneous leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome (IRIS). In May 2009, five months after the initiation of HAART therapy, he presented with ulcerative lesions on his face in association with nasal obstruction. A and B: By August 2009, the lesions progressed and severe inflammation with pronounced swelling of the lips, nasal and mentum regions are pictured. C: Computerized tomography of the paranasal sinus cavities shows partial destruction of the nasal septum (white arrow) (August, 2009). D: Healing of lesions observed following treatment with Prednisolone and Amphotericin B (September 2009).

Figure 3

Evaluation of CD4+ and CD8+ T-lymphocyte proliferation in response to soluble Leishmania antigens (SLA) in a patient with mucocutaneous leishmaniasis as manifestation of IRIS. Blood samples were collected before (August 2009) and one day following the conclusion of Amphotericin B and corticosteroid treatment (September 2009). The cell division index was calculated using Flowjo™ software. White and black bars represent the T-cell proliferative responses to Leishmania antigens prior to and after Amphotericin B treatment, respectively. Dashes represent the threshold value with respect to a positive proliferative response (above 0.06 for CD4+ T-cell and above 0.09 CD8+ T-cell subset).

Figure 4

Proportion of CD4+ and CD8+ T-cells producing intracellular IFN-γ , TNF-α and IL-10 after culturing without stimulus, and in the presence of SLA. Blood samples were collected in August 2009 from a patient with mucocutaneous leishmaniasis as manifestation of IRIS before (A) and one day after the end (B) of Amphotericin B and corticosteroid treatment (September 2009).