Abstract
Memory T-cells, particularly, effector memory T cells are implicated in the pathogenesis of inflammatory diseases and may contribute to tissue injury and disease progression. Although erythema nodosum leprosum (ENL) is an inflammatory complication of leprosy, the role of memory T cell subsets has never been studied in this patient group. The aim of this study was at investigate the kinetics of memory T cell subsets in patients with ENL before and after prednisolone treatment. A case–control study design was used to recruit 35 untreated patients with ENL and 25 non-reactional lepromatous leprosy (LL) patient controls at ALERT Hospital, Ethiopia. Venous blood samples were obtained before, during, and after treatment from each patient. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of T cell activation and memory T-cell subsets by flow cytometry. The kinetics of these immune cells in patients with ENL before and after treatment were compared with LL patient controls as well as within ENL cases at different time points. The median percentage of CD3+, CD4+, and CD8+ T-cells expressing activated T-cells were significantly higher in the PBMCs from patients with ENL than from LL patient controls before treatment. The median percentage of central and activated memory T-cells was significantly increased in patients with ENL compared to LL patient controls before treatment. Interestingly, patients with ENL had a lower percentage of naïve T cells (27.7%) compared to LL patient controls (59.5%) (P < 0.0001) before treatment. However, after prednisolone treatment, patients with ENL had a higher median percentage of naïve T-cells (43.0%) than LL controls (33.0%) (P < 0.001). The median percentage of activated T-cells (effector memory and effector T-cells) was significantly increased in patients with ENL (59.2%) before treatment compared to after treatment with prednisolone (33.9%) (P < 0.005). This is the first work which has shown T-cell activation and the different subsets of memory T cells in untreated patients with ENL. Consequently, this study delineates the role of T-cell activation in the pathogenesis of ENL reaction and challenges the long-standing dogma of immune complex as a sole etiology of ENL reaction.
Highlights
Leprosy is a disease caused by Mycobacterium leprae, an intracellular acid-fast bacillus
We described the median percentage of activated T-cells (CD62L−), total memory T-cells (CD45RO+), and the subgroups of memory T-cells before, during, and after treatment of erythema nodosum leprosum (ENL) patients and compared the results with non-reactional lepromatous leprosy (LL) patient controls as well as within ENL patients
After treatment, the frequency of activated CD8+ T-cells was significantly decreased to 34.5% in patients with ENL compared to 45.2% in LL patient controls (P ≤ 0.05; ΔHL = 10.1%) (Figure 2A)
Summary
Leprosy is a disease caused by Mycobacterium leprae, an intracellular acid-fast bacillus. It mainly infects the skin and peripheral nerves. Leprosy reactions [reversal reactions and erythema nodosum leprosum (ENL)] are immune-mediated inflammatory complications of the disease which can occur before, during, or after successful completion of multidrug treatment [2]. They cause a significant morbidity and nerve damage in leprosy patients [3]. ENL is an inflammatory complication of leprosy, manifesting as tender erythematous skin lesions and systemic features of disease including fever, neuritis, and bone pain [4]
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