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

Abstract

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.

Host immune responses induced by specific Mycobacterium leprae antigens in an overnight whole-blood assay correlate with the diagnosis of paucibacillary leprosy patients in China

“…leprae antigens in infected patients [8–14], and others focused on a panel of multiple M . leprae antigen-induced host markers by WBA [15–17]. Sampaio et al [13] reported previously that 9 of 33 M .…”

“…leprae antigens (LID-1, ML89, ML2044, and ML2028) achieved higher positive response rates in PB patients than in MB patients in Southwest China [14,15]. This marker could distinguish PB patients from tuberculosis (TB) patients after stimulation with ML2044 and ML2028, but it could not distinguish PB patients from healthy household contacts (HHC) or endemic controls (ECs) [15]. This result was consistent with those of a previous study in an Ethiopian population, in which M .…”

Measuring endemicity and burden of leprosy across countries and regions: A systematic review and Delphi survey

“…After the full-text analysis, we included 47 articles. 23 from Brazil [ 11 – 33 ], 6 from India [ 34 – 39 ], 3 from China [ 40 – 42 ], 2 from Bangladesh [ 2 , 43 ] and Comoros [ 44 , 45 ]. One from Cambodia [ 46 ], Sri-Lanka [ 47 ], Cameroon [ 48 ], Venezuela [ 49 ], Bangladesh and Thailand [ 50 ], Indonesia [ 51 ], Argentina [ 52 ], and Uganda [ 53 ].…”

Transcriptomic Analysis of Mycobacterium leprae-Stimulated Response in Peripheral Blood Mononuclear Cells Reveal Potential Biomarkers for Early Diagnosis of Leprosy

“…M. leprae could not be cultured in vitro, and acid-fast staining requires a large number of bacilli in skin biopsy, which presents low sensibility and poor specificity (Mohanty et al, 2020). Serological tests, such as the NDO-LID Rapid Test and M. leprae antigen-specific ELISA are useful tools to assist in the identification of leprosy patients, especially MB leprosy patients, and the former test has a higher sensitivity but lower specificity than the latter (Chen et al, 2018). Some new methods have been developed, such as immunological assays.…”