Antigen-specific secretion of IFNγ and CXCL10 in whole blood assay detects Mycobacterium leprae infection but does not discriminate asymptomatic infection from symptomatic leprosy

Hungria, Emerith Mayra; Freitas, Aline Araújo; Pontes, Maria Araci de Andrade; Gonçalves, Heitor S.; Sousa, Ana Lúcia Osório Maroccolo de; Costa, Maurício Barcelos; Castilho, Mirian Lane Oliveira; Duthie, Malcolm S.; Stefani, Mariane M. A.

doi:10.1016/j.diagmicrobio.2017.01.002

Cited by 10 publications

(17 citation statements)

References 38 publications

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“…Pro-inflammatory cytokines including IFN-γ are produced from activated macrophages as response to toll like receptor-2(TLR-2) signaling pathway. In active tuberculosis, serum levels of these mediators and IFN-γ levels have been proved high in patients (11).Interferon gamma is one of the most important pro-inflammatory cytokines in many infectious or noninfectious chronic inflammatory diseases, and whole blood IFNassays are popular in diagnosis of human tuberculosis (17,18,19). In the current study, the results revealed highly significant elevation in serum IFN-γ level (Table 1) in newly diagnostic TB patients, relapse TB patients and healthy controls (P<0.001and P<0.014, respectively).…”

Section: Discussion: Serum Ifn-γ Levelmentioning

confidence: 99%

DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

al.¹

2019

Baghdad Sci.J

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Tuberculosis (TB) still remains an important medical problem due to high levels of morbidity and mortality worldwide. A series of innate immune mechanisms that create a cytokine network control the pathogenesis of tuberculosis and this response has the capacity to modify the host genomic DNA structure through epigenetic mechanisms such as DNA methylation which could constantly alter the local gene expression pattern that can modulate the metabolism of the tissues and the immune-response. Interferon-gamma (IFN-γ) is an important pro-inflammatory cytokine regulator of the innate immune response to TB. This study aims to determine DNA methylation patterns of INF-γ gene promoter and measure serum IFN- γ level in newly diagnosed TB patients, relapse TB patients, and healthy control, in order to study the possibility of using these as a biomarker for the prognosis of TB stages in patients. The current case-control study included 66 patients with TB and 33 healthy control subjects. DNA was extracted from peripheral blood(PB) of included subjects and modified using sodium bisulfate specific kit. DNA methylation patterns of IFN-γ gene promoter was determine by using methylation specific polymerase chain reaction(MS-PCR).Serum IFN-γ level was determined using enzyme linked immune-sorbent assay(ELISA). Results showed that percentages of DNA methylation patterns in normal controls, newly diagnostic TB patients and relapse TB patients were (63.3%, 18.2% and 21.2% respectively). Also, higher significant differences (P≤0.0001) of un-methylated IFN-γ gene promoter patterns in newly diagnostic TB patients than relapse TB patients comparison with healthy controls. The percentage of un-methylated DNA patterns in healthy controls, newly diagnostic TB patients and relapse TB patients were (9.9%, 39.4% and 51.5%, respectively). The mean of serum IFN-γ levels (pg/ml) for normal controls, newly diagnostic TB patients and relapse TB patients were (59.3± 13.8,75.8±24.3 and 69.6±18.7,respectively).In conclusion, there is a relative association between methylation of IFN-γ gene promoter and predisposing to TB progression.

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Section: Discussion: Serum Ifn-γ Levelmentioning

confidence: 99%

DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

al.¹

2019

Baghdad Sci.J

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“…leprae recombinant protein (rML)(LID-1), M . leprae diffusion proteins[46f(ML0405+ML0568) and 73f(ML2028+ML2346+ML2044)] and combinations of rML (46f+LID-1, ML0276+LID-1, ML2055+ML1632+ML2044, ML0276+46f, and ML2055+LID-1) were used in these studies[ 20 , 28 – 31 ]. IFN-γ and CXCL10 were evaluated as potential diagnostic host markers for PB leprosy patients in the hyper-endemic regions of Brazil[ 20 , 28 – 31 ] and China[ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…leprae diffusion proteins[46f(ML0405+ML0568) and 73f(ML2028+ML2346+ML2044)] and combinations of rML (46f+LID-1, ML0276+LID-1, ML2055+ML1632+ML2044, ML0276+46f, and ML2055+LID-1) were used in these studies[ 20 , 28 – 31 ]. IFN-γ and CXCL10 were evaluated as potential diagnostic host markers for PB leprosy patients in the hyper-endemic regions of Brazil[ 20 , 28 – 31 ] and China[ 15 ]. Newly diagnosed PB patients produced more IFN-γ than MB patients[ 28 – 31 ], and IFN-γ was helpful in the differential diagnosis of leprosy from other confounding dermatoses[ 2 ].…”

Section: Discussionmentioning

confidence: 99%

“…IFN-γ and CXCL10 were evaluated as potential diagnostic host markers for PB leprosy patients in the hyper-endemic regions of Brazil[ 20 , 28 – 31 ] and China[ 15 ]. Newly diagnosed PB patients produced more IFN-γ than MB patients[ 28 – 31 ], and IFN-γ was helpful in the differential diagnosis of leprosy from other confounding dermatoses[ 2 ]. CXCL10 discriminated PB from EC only in ML0276+LID-1 WBA; however, CXCL10 could not discriminate active disease (PB) from HHC individuals[ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Newly diagnosed PB patients produced more IFN-γ than MB patients[ 28 – 31 ], and IFN-γ was helpful in the differential diagnosis of leprosy from other confounding dermatoses[ 2 ]. CXCL10 discriminated PB from EC only in ML0276+LID-1 WBA; however, CXCL10 could not discriminate active disease (PB) from HHC individuals[ 28 ]. In this study, we also demonstrated that for new cases, PB patients produced more IFN-γ than MB patients; however, IFN-γ did not discriminate active disease (PB) from HHC or EC individuals.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of antigen-specific immune responses for leprosy diagnosis in a hyperendemic area in China

et al. 2018

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ObjectiveTo evaluate antigen-specific immune responses for leprosy diagnosis in a hyperendemic area in China.MethodsEighty-three leprosy patients and 161 non-leprosy controls were enrolled from Hani-yi Autonomous Prefecture of Honghe, Yunnan Province, China. Leprosy patients were divided into multibacillary (MB, n = 38), paucibacillary (PB, n = 23), and post-multi-drug therapy (MDT, n = 22) groups. Controls were divided into the following groups: healthy household contacts (HHC, n = 119), tuberculosis (TB, n = 11), and endemic controls (EC, n = 31). The NDO-LID Rapid Test, M. leprae antigen-specific ELISA and antigen-specific IFN-γ secretion in a whole blood assay (WBA) were used to evaluate these subjects.ResultsThe NDO-LID Rapid Test achieved higher positive response rates in MB than in PB patients[94.7%(36/38) vs 65.2%(15/23)], and these rates were higher than those observed by ELISA using anti-LID-1[92.1%(35/38) vs 52.2%(12/23)], anti-NDO-LID[92.1%(35/38) vs 47.8% (11/23)], and anti-ND-O-BSA[89.5%(34/38) vs 60.9%(14/23)]. However, the NDO-LID Rapid Test also showed a higher positive response rate in the EC group (33.3%,10/31), which was higher than the rates observed for anti-NDO-LID (12.9%,4/31) and anti-ND-O-BSA (16.1%,5/31). M. leprae antigen-specific ELISA demonstrated relatively high specificity (86.84–97.37%) but low sensitivity (15.97–72.73%) in discriminating between leprosy patients and non-leprosy controls by ROC curve analysis. In contrast, M. leprae antigen-specific IFN-γ secretion detection achieved higher positive response rates in PB than in MB patients (positive ratio of MB vs PB: 40% vs 56% for LID-1, 28.6% vs 47.8% for ML89, 31.4% vs 60.7% for ML2044, and 31.4 vs 47.8% for ML2028) and could distinguish MB from EC when stimulated with ML89(AUC = 0.6664) and PB fromTB when stimulated with ML2044 and ML2028(AUC = 0.7549 and 0.7372, respectively).ConclusionThe NDO-LID Rapid Test and M. leprae antigen-specific ELISA are useful tools to assist in the diagnosis of leprosy patients, especially MB patients, although the former had higher sensitivity but lower specificity than the latter. M. leprae antigen-specific IFN-γ release assessed by WBA has diagnostic value for distinguishing PB from TB but not for distinguishing PB from HHC or EC. Screening novel M. leprae-specific antigens, combining different M. leprae antigens and a multi-cytokine analyte model may be needed for more effective diagnosis of leprosy.

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Leprosy surveillance study in a highly endemic Brazilian area using leprosy specific serologic tests and IFNγ whole blood assay

Gonçalves

Hungria

Freitas

et al. 2020

Eur J Clin Microbiol Infect Dis

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Antigen-specific secretion of IFNγ and CXCL10 in whole blood assay detects Mycobacterium leprae infection but does not discriminate asymptomatic infection from symptomatic leprosy

Cited by 10 publications

References 38 publications

DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

Evaluation of antigen-specific immune responses for leprosy diagnosis in a hyperendemic area in China

Leprosy surveillance study in a highly endemic Brazilian area using leprosy specific serologic tests and IFNγ whole blood assay

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