Number of leprosy reactions during treatment: clinical correlations and laboratory diagnosis

Antunes, Douglas Eulálio; Ferreira, Gabriela Porto; Nicchio, Mariana Vitorino Candeiro; Araujo, Sergio; Cunha, Ana Carolina Rodrigues da; Gomes, Rafaela Resende; Costa, Anaíra Ribeiro Guedes Fonseca; Goulart, Isabela Maria Bernardes

doi:10.1590/0037-8682-0440-2015

Cited by 10 publications

(15 citation statements)

References 12 publications

(11 reference statements)

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“…Higher levels of anti-LAM in the leprosy reaction group is due to the presence of great number of individuals with ENL, since LAM is involved in the formation of immune complexes and in the pathogenesis of erythema nodosum leprosum [39]. High levels of anti-PGL-I in leprosy reactions, independently on the type of reaction, ratify that this antigen is a risk marker for the occurrence of reactions, during treatment and after discharge from MDT, corroborating with previous studies that showed positive serology anti-PGL-I as a risk factor to the reactional condition [3, 7, 40].…”

Section: Discussionsupporting

confidence: 82%

Differential Expression of IFN-γ, IL-10, TLR1, and TLR2 and Their Potential Effects on Downgrading Leprosy Reaction and Erythema Nodosum Leprosum

Antunes

Goulart

Lima

et al. 2019

Journal of Immunology Research

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Leprosy reactions are acute immunological events that occur during the evolution of chronic infectious disease causing neural damage and disabilities. A study using blood samples of 17 leprosy reaction patients and 17 reaction-free was carried out by means of associations between antigens, receptors, and expression of cytokines, using path analysis providing new insights into the immunological mechanisms involved in triggering leprosy reactions. Toll-like receptors (TLR) such as TLR1 and TLR2, presented balanced expression in the reaction-free multibacillary (MB) group (TLR1: 1.01 ± 0.23, TLR2: 1.22 ± 0.18; p = 0.267). On the other hand, downgrading type 1 reaction (T1R) (TLR1: 1.24 ± 0.17, TLR2: 2.88 ± 0.37; p = 0.002) and erythema nodosum leprosum (ENL) (TLR1: 1.93 ± 0.17, TLR2: 2.81 ± 0.15; p = 0.004) revealed an unbalance in relation to the expression of these receptors. When the path analysis was approached, it was noted that interleukin 10 (IL-10) expression showed a dependence relation with phenolic glycolipid I (PGL-I) in downgrading T1R (direct effect = 0.503 > residual effect = 0.364), whereas in ENL, such relationship occurred with lipoarabinomannan (LAM) (direct effect = 0.778 > residual effect = 0.280). On the contrary, in the reaction-free leprosy group, interferon-gamma (IFN-γ) levels were dependent on the association between TLR2 and TLR1 (0.8735). The high TLR2 expression associated with IL-10 levels, in the leprosy reaction groups, may be hypothetically related to the formation of TLR2/2 homodimers and/or TLR2/6 heterodimers linked to evasion mechanisms in downgrading reactions and pathophysiology of ENL.

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“…Dynamic and unpredictable episodes of increased inflammation, leprosy reactions, can occur before, during and even after treatment, with a higher likelihood to occur in adults than in children 9,10 . These immunological complications are the principal cause of leprosy-associated irreversible neuropathy and are experienced by 30–50% of leprosy patients one or more times, mostly in the unstable borderline lepromatous patients with substantial bacterial loads 11 . Two types of reactions are recognized: reversal reactions or type 1 (RR) and erythema nodosum leprosum (ENL).…”

Section: Introductionmentioning

confidence: 99%

Whole blood RNA signatures in leprosy patients identify reversal reactions before clinical onset: a prospective, multicenter study

Tió-Coma

Hooij

Bobosha

et al. 2019

Sci Rep

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Early diagnosis of leprosy is challenging, particularly its inflammatory reactions, the major cause of irreversible neuropathy in leprosy. Current diagnostics cannot identify which patients are at risk of developing reactions. This study assessed blood RNA expression levels as potential biomarkers for leprosy. Prospective cohorts of newly diagnosed leprosy patients, including reactions, and healthy controls were recruited in Bangladesh, Brazil, Ethiopia and Nepal. RNA expression in 1,090 whole blood samples was determined for 103 target genes for innate and adaptive immune profiling by dual color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification (dcRT-MLPA) followed by cluster analysis. We identified transcriptomic biomarkers associated with leprosy disease, different leprosy phenotypes as well as high exposure to Mycobacterium leprae which respectively allow improved diagnosis and classification of leprosy patients and detection of infection. Importantly, a transcriptomic signature of risk for reversal reactions consisting of five genes (CCL2, CD8A, IL2, IL15 and MARCO) was identified based on cross-sectional comparison of RNA expression. In addition, intra-individual longitudinal analyses of leprosy patients before, during and after treatment of reversal reactions, indicated that several IFN-induced genes increased significantly at onset of reaction whereas IL15 decreased. This multi-site study, situated in four leprosy endemic areas, demonstrates the potential of host transcriptomic biomarkers as correlates of risk for leprosy. Importantly, a prospective five-gene signature for reversal reactions could predict reversal reactions at least 2 weeks before onset. Thus, transcriptomic biomarkers provide promise for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.

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“…These result from changes to the immune balance between the host and M . leprae that lead to increased morbidity and impairment of peripheral nerve function [7, 8, 9].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the cutaneous sensation of the face in patients with different clinical forms of leprosy

et al. 2019

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BackgroundLeprosy can be considered to be the most common peripheral neuropathy of infectious etiology and constitutes a public health problem. The standard routine examination for assessing sensory impairment in leprosy neuropathy basically evaluates hands, feet and eyes. However, evaluation of facial cutaneous sensation is not routinely performed.ObjectivesThe aim of this study was to evaluate facial cutaneous sensation in patients with different clinical forms of leprosy and compare the findings with those from healthy individuals.Methodology19 healthy controls and 71 leprosy patients who were being treated at a national reference center for leprosy in Brazil underwent facial sensation assessment using the Semmes-Weinstein monofilament test. This test was applied over the facial areas corresponding to the ophthalmic, maxillary and mandibular distal branches of the trigeminal nerve.ResultsThe predominant clinical form in terms of changes to facial cutaneous sensation was lepromatous leprosy (LL), followed by the borderline-borderline (BB), and borderline-lepromatous (BL) forms, in comparison with healthy individuals. The distal branches most affected were the zygomatic (28.2%; 20/71), buccal (23.9%; 17/71) and nasal (22.5%; 16/71). There was asymmetrical sensory impairment of the face in 62.5% (20/32) of the cases.ConclusionThe face is just as impaired in leprosy as are the feet, hands and eyes, but facial impairment is underdiagnosed. Our evaluation on the different sensory branches and evidence of asymmetrical impairment of the face confirm the classically described pattern of leprosy neuropathy, i.e. consisting of asymmetrical and predominantly sensory peripheral neuropathy.

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“…Como foi observada nesse estudo, a maior quantidade de lesões cutâneas inspecionadas no diagnóstico, utilizada para fins de classificação operacional dos pacientes, mostrou-se como variável associada ao grupo reacional, funcionando como um caracterizador desses indivíduos MB, visto que, esse dado clínico é um indicador da presença de elevados níveis de antígenos nesses pacientes. Trabalhos anteriores do nosso grupo corroboram com esse resultado do presente estudo, haja vista que, demonstraram uma correlação positiva entre a quantidade de lesões cutâneas no diagnóstico com o número de reações hansênicas desenvolvidas durante o tratamento (ANTUNES et al, 2016), bem como o IB do diagnóstico e o número de reações durante e após o tratamento (RODRIGUES et al, 2000).…”

Section: Dados Clínicos E Epidemiológicosunclassified

“…Existem estudos relatando a associação de risco existente entre os níveis do antígeno PGL-1 e as reações do tipo 2 (ENH) (MANANDHAR; LEMASTER; ROCHE, 1999), além de evidencias sobre a participação do PGL-1 na patogênese do ENH e na formação de imunocomplexos (ROJAS et al, 1997). Além disso, vários trabalhos demonstraram que pacientes com sorologia ELISA anti-PGL-1 positiva no diagnóstico tiveram maior risco para ocorrência de reações, durante o tratamento e após alta da PQT (BRITO et al, 2008;ANTUNES et al, 2013;ANTUNES et al, 2016).…”

Section: Os Níveis De Anti-pgl-1 E Anti-lam Nos Grupos Reacionais E Cunclassified

Relações causais entre os antígenos de M. leprae (LAM E PGL-1) e os receptores TOLL-LIKE 1, 2 e seus efeitos na expressão de citocinas IFN-γ e IL-10 nas reações hansênicas

Antunes¹

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Background: The leprosy reactions are acute immunological events that occur before, during or after MDT of leprosy, being triggered mainly by interaction between the antigens of Mycobacterium leprae, PGL-1 and LAM, with the components of immunity of the host, such as, TLR1 and TLR2, that induce cells to produce cytokines related to control or bacillary dissemination. Objectives: The main goal of this research is establish causal relations between antigens of M. leprae (PGL-1 and LAM) and receptors, TLR1, TLR2 and their effects on cytokines expression, IFN-10, in leprosy reactions. Methods: Through ELISA serology it was possible measure the levels of anti-PGL-1 IgM and anti-LAM IgG, and with the use of the RT-qPCR proceeded the analysis of gene expression of TLR1 TLR2, IFN-10 using blood samples from 17 reactional patients and 17 nonreactional patients (Case-control study) that posteriorly were subdivided into 4 groups. For comparison between means of the variables, it resorted to use of analysis of variance (ANOVA) and about the degree of association between the variables, it has applied the correlation matrix. At the end, it was used the path analysis to verify the causal relation evolving antigens and toll-like receptors, whose the direct and indirect effects were the cytokines expression. Results: Among 34 patients, 76.4% (26/34) were MB and 23.6% PB, being that 100% (17/17) of reactional cases were MB and among the controls 53% (9/17). Analyzing the reactional group, 41.2% (7/17) suffered type 1 reaction, while 58.8% (10/17) presented type 2 reaction, emphasizing that, among patients with type 1 reaction, 57.1% (4/7) had reaction before treatment (downgrading), 14.2% (1/7) during and 28.8% (2/7) after MDT, whereas all patients of the type 2 reaction group, developed this occurrence after treatment. The levels of anti-PGl-1 have been elevated in type 1 and type 2 reactions with significant differences between means of these groups when compared to PB controls (F=6.42; p=0.002). Regarding to anti-LAM, this has been associated to type 2 reaction, group whose the means were higher than others, and this data showed significant differences as well (F=15.27; p<0.001). The reactional groups expressed higher levels of IL-10 (F=3.99; p=0,023), whereas the control group produced high levels of IFN-, especially the PB control (F=5.30; p=0.008). There were no differences in the levels of TLR1 and TLR2 expression in the comparison among groups. In the reactional group, the path analysis quantified the direct effects of anti-LAM (0.623) e anti-PGL-1 (0.605) on TLR2, which were higher than the residual effect of this model (0.255), indicating that these antigenic markers influenced only the TLR2 expression, which consequently correlated with the IL-10 expression in this group. An opposing mechanism occurred in the control group, insofar as it was found an immunological pathway that regulated the IFN-expression dependent on TLR1 and TLR2 association. Conclusion: In conclusion, path analysis allowed to demonstrate the causal r...

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Number of leprosy reactions during treatment: clinical correlations and laboratory diagnosis

Cited by 10 publications

References 12 publications

Differential Expression of IFN-γ, IL-10, TLR1, and TLR2 and Their Potential Effects on Downgrading Leprosy Reaction and Erythema Nodosum Leprosum

Whole blood RNA signatures in leprosy patients identify reversal reactions before clinical onset: a prospective, multicenter study

Evaluation of the cutaneous sensation of the face in patients with different clinical forms of leprosy

Relações causais entre os antígenos de M. leprae (LAM E PGL-1) e os receptores TOLL-LIKE 1, 2 e seus efeitos na expressão de citocinas IFN-γ e IL-10 nas reações hansênicas

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