Abstract
Leprosy reactions are acute inflammatory episodes that complicate the course of a Mycobacterium leprae infection and are the major cause of leprosy-associated pathology. Two types of leprosy reactions with relatively distinct pathogenesis and clinical features can occur: type 1 reaction, also known as reversal reaction, and type 2 reaction, also known as erythema nodosum leprosum. These acute nerve-destructive immune exacerbations often cause irreversible disabilities and deformities, especially when diagnosis is delayed. However, there is no diagnostic test to detect or predict leprosy reactions before the onset of clinical symptoms. Identification of biomarkers for leprosy reactions, which impede the development of symptoms or correlate with early-onset, will allow precise diagnosis and timely interventions to greatly improve the patients' quality of life. Here, we review the progress of research aimed at identifying biomarkers for leprosy reactions, including its correlation with not only immunity but also genetics, transcripts, and metabolites, providing an understanding of the immune dysfunction and inflammation that underly the pathogenesis of leprosy reactions. Nevertheless, no biomarkers that can reliably predict the subsequent occurrence of leprosy reactions from non-reactional patients and distinguish type I reaction from type II have yet been found.
Highlights
LeprosyLeprosy, known as Hansen’s disease, is an age-old disease, and patients with leprosy have been ostracized by their communities and families throughout history [1,2,3]
Compared with non-reactional patients, enhanced Th1 responses and macrophage activation in type 1 reaction (T1R) is demonstrated by a proinflammatory Th1 cytokine profile, including IFN-γ, tumor necrosis factor (TNF)-α, IL-1β, IL-6, IL-2, soluble IL-2 receptors, IL-12, transforming growth factor (TGF)-β, and inducible nitric oxide synthase, in the blood, skin, and nerves [62,63,64]
As Lipoxin A4 (LXA4) and resolvin D1 (RvD1) are predominant in non-reactional leprosy patients, it is speculated that they play a role in the maintenance of the disease, avoiding exacerbated inflammatory responses, which could be deleterious for both the pathogen and host [98, 125]
Summary
Two types of leprosy reactions with relatively distinct pathogenesis and clinical features can occur: type 1 reaction, known as reversal reaction, and type 2 reaction, known as erythema nodosum leprosum. These acute nerve-destructive immune exacerbations often cause irreversible disabilities and deformities, especially when diagnosis is delayed. There is no diagnostic test to detect or predict leprosy reactions before the onset of clinical symptoms. Identification of biomarkers for leprosy reactions, which impede the development of symptoms or correlate with early-onset, will allow precise diagnosis and timely interventions to greatly improve the patients’ quality of life.
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