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. 2015 Oct 23;9(10):e0004179.
doi: 10.1371/journal.pntd.0004179. eCollection 2015.

Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients

Eugenia Carrillo  1 , Nerea Carrasco-Antón  2 , Francisco López-Medrano  2 , Efrén Salto  3 , Laura Fernández  1 , Juan Víctor San Martín  4 , Jorge Alvar  5 , Jose María Aguado  2 , Javier Moreno  1
Affiliations

Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients

Eugenia Carrillo et al. PLoS Negl Trop Dis. .

Abstract

Spain has one of the world's largest pools of organ donors and is a global leader in terms of the number of transplants it performs. The current outbreak of leishmaniasis in Fuenlabrada (in the southwest of the region of Madrid, Spain) has involved 600 clinical cases since late 2009 (prevalence 0.2%). It may therefore be wise to monitor the town's transplanted population for Leishmania infantum; its members are immunosuppressed and at greater risk of infection and relapse following treatment. The present work examines the use of cytokine release assays to determine the prevalence of Leishmania infection in this population, and to confirm recovery following treatment for visceral leishmaniasis (VL). The humoral and cellular immune responses to L. infantum were characterized in 63 solid organ transplant (SOT) recipients from Fuenlabrada, 57 of whom reported no previous episode of VL (NVL subjects), and six of whom had been cured of VL (CVL subjects). Seventeen subjects (12 NVL and 5 CVL) showed a patent lymphoproliferative response to soluble Leishmania antigen (SLA). Stimulation of peripheral blood mononuclear cell cultures and of whole blood with SLA led to the production of different combinations of cytokines that might serve to confirm Leishmania infection or recovery from VL and help prevent cured patients from relapsing into this serious condition.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Lymphoproliferative response to SLA of PBMCs from solid organ (SOT) recipients—57 with no previous history of leishmaniasis (NVL) and 5 cured SOT recipients (CVL).
NVL SOT recipients were then classified as either positive (NVLlp+) or negative (NVLlp-). ***p<0.001.
Fig 2
Fig 2. Cytokine and granzyme B production after PBMC stimulation with SLA for 5 days.
IFN-γ, granzyme B, TNF-α, IL-10, IL-5, IL-17A, IL-2 and IL-4 concentrations (pg/ml) were measured in culture supernatants of 12 NVLlp+ subjects, 7 NVLlp- subjects, and 5 CVL subjects. *p<0.05, **p<0.01, ***p<0.001.
Fig 3
Fig 3. Linear regression for granzyme B and IFN-γ in SLA-stimulated PBMCs from NVLlp+ subjects.
A significant correlation was found between these variables (r = 0.818, P = 0.00093).
Fig 4
Fig 4. Cytokine and granzyme B production in whole blood plasma in response to SLA stimulation for 24 h.
The IFN-γ, granzyme B, TNF-α, IL-10 and IL-2 concentrations (pg/ml) were measured for 12 NVLlp+ subjects, 7 NVLlp- subjects, and 5 CVL subjects. *p<0.05, **p<0.01, ***p<0.001.
Fig 5
Fig 5. Linear regression of IFN-γ and IL-2 responses in plasma from SLA-stimulated whole blood plasma in NVLlp+ subjects.
A significant correlation was detected between these variables (r = 0.616, P = 0.018).
Fig 6
Fig 6. Linear regression of stimulation index and IFN-γ in plasma from SLA-stimulated whole blood plasma from NVLlp+ subjects.
A significant correlation was detected between these variables (r = 0.881, P = 0.002).
See this image and copyright information in PMC

References

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