In search of biomarkers for leprosy by unraveling the host immune response to <i>Mycobacterium leprae</i>

Hooij, Anouk van; Geluk, Annemieke

doi:10.1111/imr.12966

Cited by 36 publications

(29 citation statements)

References 156 publications

(273 reference statements)

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“…IgA antibodies to M. leprae are found in saliva and blood. Van Hooij & Geluk (2021) demonstrated that contacts of untreated leprosy patients show higher salivary IgA levels in response to either LAM or PGL-I than endemic controls ( 6 ). De Macedo et al strongly recommended anti-PGL-I IgA as a biomarker adjunct to anti-PGL-I IgM for serological and clinical follow-up studies of household leprosy contacts in high endemical areas ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

“…The diagnosis of leprosy is hampered by the broad spectrum of clinical forms dictated by the host's immune response to M. leprae , ranging from disseminated infection to a self-limited form of the disease, with lack of effective testing available to detect asymptomatic infection or predict disease progression ( 6 ). In this context, the search for immune biomarkers of infection has been focused upon specific antibodies.…”

Section: Introductionmentioning

confidence: 99%

“…In this context, the search for immune biomarkers of infection has been focused upon specific antibodies. Although serology is not used routinely, it has been widely explored in research studies since the discovery of the phenolic glycolipid antigen I (PGL-I), a cell wall antigen of M. leprae which induces the production of specific IgM response detected in patient serum ( 6 ). Despite nearly all MB leprosy patients being positive for anti-PGL-I IgM responses, most PB leprosy patients do not develop detectable antibody levels against PGL-I ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

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Serum IgA Antibodies Specific to M. leprae Antigens as Biomarkers for Leprosy Detection and Household Contact Tracking

et al. 2021

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Leprosy remains endemic in several developing countries, such as India and Brazil, in part due to delayed diagnosis that facilitates ongoing transmission. Although immunoglobulins against several Mycobacterium leprae antigens have been indicated for the early diagnosis, and IgA participates in the early stages of leprosy and in subclinical infection, relatively little research has examined anti-M. leprae IgA responses. Here, we investigated serum IgA reactivity against NDO-HSA, LID-1 and NDO-LID, in paucibacillary (PB) and multibacillary (MB) patients and their household contacts, using enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy of each ELISA was evaluated by receiver operating characteristic (ROC) curve analysis. Our data reveal elevated IgA serum levels against the three M. leprae specific antigens in MB patients, whereas IgA reactivity in PB patients was increased only to NDO-HSA. Further, MB and PB household contacts displayed higher IgA reactivity to NDO-HSA than non-endemic controls. Our data suggest measurement of serum IgA against NDO-HSA as an additional tool in the diagnosis and classification of the disease, with potential utility for household contact follow-up.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum IgA Antibodies Specific to M. leprae Antigens as Biomarkers for Leprosy Detection and Household Contact Tracking

et al. 2021

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“…Characteristic for leprosy is its disease spectrum, with on one end tuberculoid leprosy (TT) associated with Th1 and Th17 T cell immune responses, and on the other end lepromatous leprosy (LL) (Hungria et al, 2018;van Hooij and Geluk, 2021), the more severe type of leprosy with disseminated infection generally linked to anti-inflammatory Th2 responses (Salgame et al, 1991;Quaresma et al, 2015;Aarão et al, 2016). Moreover, LL patients, also referred to as multibacillary (MB) leprosy, display well detectable antibody levels, in particular IgM directed against M. leprae PGL-I, whereas IgG and IgA are detected mostly in lower levels.…”

Section: Introductionmentioning

confidence: 99%

Detection and Monitoring of Mycobacterium leprae Infection in Nine Banded Armadillos (Dasypus novemcinctus) Using a Quantitative Rapid Test

et al. 2021

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Leprosy is an infectious disease caused by Mycobacterium leprae with tropism for skin and peripheral nerves. Incessant transmission in endemic areas is still impeding elimination of leprosy. Although detection of M. leprae infection remains a challenge in asymptomatic individuals, the presence of antibodies specific for phenolglycolipid-I (PGL-I) correlate with bacterial load. Therefore, serosurveillance utilizing field-friendly tests detecting anti-PGL-I antibodies, can be applied to identify those who may transmit bacteria and to study (reduction of) M. leprae transmission. However, serology based on antibody detection cannot discriminate between past and present M. leprae infection in humans, nor can it detect individuals carrying low bacillary loads. In humans, anti-PGL-I IgM levels are long-lasting and usually detected in more individuals than anti-PGL-I IgG levels. Inherent to the characteristically long incubation time of leprosy, IgM/IgG relations (antibody kinetics) in leprosy patients and infected individuals are not completely clear. To investigate the antibody response directly after infection, we have measured antibody levels by ELISA, in longitudinal samples of experimentally M. leprae infected, susceptible nine-banded armadillos (Dasypus novemcinctus). In addition, we assessed the user- and field-friendly, low-cost lateral flow assay (LFA) utilizing upconverting reporter particles (UCP), developed for quantitative detection of human anti-PGL-I IgM (UCP-LFA), to detect treatment- or vaccination-induced changes in viable bacterial load. Our results show that serum levels of anti-PGL-I IgM, and to a lesser extent IgG, significantly increase soon after experimental M. leprae infection in armadillos. In view of leprosy phenotypes in armadillos, this animal model can provide useful insight into antibody kinetics in early infection in the various spectral forms of human leprosy. The UCP-LFA for quantitative detection of anti-PGL-I IgM allows monitoring the efficacy of vaccination and rifampin-treatment in the armadillo leprosy model, thereby providing a convenient tool to evaluate the effects of drugs and vaccines and new diagnostics.

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“…As has become clear from biomarker research for mycobacterial diseases TB and leprosy, the use of combined analysis of biomarkers through a biomarker signature improves sensitivity and specificity for diagnosis [ 28 , 35 , 36 ]. In this respect, host protein biomarker signatures were identified that distinguished active, pulmonary TB patients from other respiratory diseases (ORD) amongst primary healthcare clinic attendees in Africa with signs and symptoms suggestive of TB [ 37 , 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates

Zhou

Hooij

Vervenne

et al. 2021

Biology

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Nonhuman primates (NHPs) are relevant models to study the pathogenesis of tuberculosis (TB) and evaluate the potential of TB therapies, but rapid tools allowing diagnosis of active pulmonary TB in NHPs are lacking. This study investigates whether low complexity lateral flow assays utilizing upconverting reporter particles (UCP-LFAs) developed for rapid detection of human serum proteins can be applied to detect and monitor active pulmonary TB in NHPs. UCP-LFAs were used to assess serum proteins levels and changes in relation to the MTB challenge dosage, lung pathology, treatment, and disease outcome in experimentally MTB-infected macaques. Serum levels of SAA1, IP-10, and IL-6 showed a significant increase after MTB infection in rhesus macaques and correlated with disease severity as determined by pathology scoring. Moreover, these biomarkers could sensitively detect the reduction of bacterial levels in the lungs of macaques due to BCG vaccination or drug treatment. Quantitative measurements by rapid UCP-LFAs specific for SAA1, IP-10, and IL-6 in serum can be utilized to detect active progressive pulmonary TB in macaques. The UCP-LFAs thus offer a low-cost, convenient, and minimally invasive diagnostic tool that can be applied in studies on TB vaccine and drug development involving macaques.

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In search of biomarkers for leprosy by unraveling the host immune response to Mycobacterium leprae

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 36 publications

References 156 publications

Serum IgA Antibodies Specific to M. leprae Antigens as Biomarkers for Leprosy Detection and Household Contact Tracking

Serum IgA Antibodies Specific to M. leprae Antigens as Biomarkers for Leprosy Detection and Household Contact Tracking

Detection and Monitoring of Mycobacterium leprae Infection in Nine Banded Armadillos (Dasypus novemcinctus) Using a Quantitative Rapid Test

Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates

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