02729nas a2200301 4500000000100000008004100001260001200042653000800054653001400062653001200076653003000088653002100118653001600139100001600155700002000171700001300191700001200204700001400216700001100230700001100241700001600252700001700268700001200285245012200297856008300419520191100502022001402413 2021 d c10/202110aBCG10aCytokines10aleprosy10aPost exposure prophylaxis10aTrained immunity10aVaccination1 avan Hooij A1 avan den Eeden S1 aKhatun M1 aSoren S1 aFranken K1 aRoy JC1 aAlam K1 aChowdhury A1 aRichardus JH1 aGeluk A00aBCG-induced immunity profiles in household contacts of leprosy patients differentiate between protection and disease. uhttps://www.sciencedirect.com/science/article/pii/S0264410X21013487?via%3Dihub3 a
Leprosy is an infectious disease caused by Mycobacterium leprae leading to irreversible disabilities along with social exclusion. Leprosy is a spectral disease for which the clinical outcome after M. leprae infection is determined by host factors. The spectrum spans from anti-inflammatory T helper-2 (Th2) immunity concomitant with large numbers of bacteria as well as antibodies against M. leprae antigens in multibacillary (MB) leprosy, to paucibacillary (PB) leprosy characterised by strong pro-inflammatory, Th1 as well as Th17 immunity. Despite decades of availability of adequate antibiotic treatment, transmission of M. leprae is unabated. Since individuals with close and frequent contact with untreated leprosy patients are particularly at risk to develop the disease themselves, prophylactic strategies currently focus on household contacts of newly diagnosed patients. It has been shown that BCG (re)vaccination can reduce the risk of leprosy. However, BCG immunoprophylaxis in contacts of leprosy patients has also been reported to induce PB leprosy, indicating that BCG (re)vaccination may tip the balance between protective immunity and overactivation immunity causing skin/nerve tissue damage. In order to identify who is at risk of developing PB leprosy after BCG vaccination, amongst individuals who are chronically exposed to M. leprae, we analyzed innate and adaptive immune markers in whole blood of household contacts of newly diagnosed leprosy patients in Bangladesh, some of which received BCG vaccination. As controls, individuals from the same area without known contact with leprosy patients were similarly assessed. Our data show the added effect of BCG vaccination on immune markers on top of the effect already induced by M. leprae exposure. Moreover, we identified BCG-induced markers that differentiate between protective and disease prone immunity in those contacts.
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