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2017 ; 11
(10
): e0006001
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T-cell regulation in Erythema Nodosum Leprosum
#MMPMID28991896
Negera E
; Walker SL
; Bobosha K
; Howe R
; Aseffa A
; Dockrell HM
; Lockwood DN
PLoS Negl Trop Dis
2017[Oct]; 11
(10
): e0006001
PMID28991896
show ga
Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum
correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is
an immune-mediated inflammatory complication, which causes significant morbidity
in affected leprosy patients. The underlying cause of ENL is not conclusively
known. However, immune-complexes and cell-mediated immunity have been suggested
in the pathogenesis of ENL. The aim of this study was to investigate the
regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL
and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT
Hospital, Ethiopia were enrolled to the study. Blood samples were obtained
before, during and after prednisolone treatment of ENL cases. Peripheral blood
mononuclear cells (PBMCs) were isolated and used for immunophenotyping of
regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27
and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and
histopathological data were obtained as supplementary information. All patients
had been followed for 28 weeks. Patients with ENL reactions had a lower
percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at
diagnosis of ENL before treatment. After treatment, the percentage of
CD4+regulatory T-cells was not significantly different between the two groups.
The percentage of CD8+ regulatory T-cells was not significantly different in ENL
and LL controls before and after treatment. Furthermore, patients with ENL had
higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient
controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was
not significantly different in ENL and LL controls suggesting that CD25
expression is not associated with ENL reactions while FoxP3 expression on CD4+
T-cells was significantly lower in patients with ENL than in LL controls. We also
found that prednisolone treatment of patients with ENL reactions suppresses CD4+
T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower
levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that
this loss of regulation is one of the causes of ENL.