Evaluation of various cytokines elicited during antigen-specific recall as potential risk indicators for the differential development of leprosy

Abstract

Leprosy is a dermato-neurological disease caused by Mycobacterium leprae infection that manifests across a wide range of clinical and immunological outcomes. Diagnosis is still currently based on clinical manifestations and simple tests are needed. This study investigated whether biomarkers induced by defined M. leprae proteins in 24-h whole blood assays (WBA) could discriminate active leprosy patients from at-risk contacts. Newly diagnosed, untreated paucibacillary (PB; tuberculoid leprosy/borderline tuberculoid [TT/BT]) and multibacillary (MB; borderline lepromatous/lepromatous leprosy [BL/LL]) leprosy patients, as well as healthy household contacts (HHC) of MB patients, were recruited in central western Brazil (Goiânia/Goiás). Cell-based responses to the ML0276, ML1623, ML0405, ML1632, 92f, and ML1011 antigens were measured by Luminex 14-plex assays detecting eotaxin, IFNγ, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-15, IL-17A, IL-23, IL-31, IP-10, and TNFα. Our data reinforce that IFNγ is currently the best indicator of the antigen-specific cellular immune response of TT/BT leprosy and demonstrate that the same antigens promote the secretion of IL-4 in blood from BL/LL leprosy patients. While none of the biomarkers tested could discriminate leprosy patients from HHC, our data indicate that, although most HHC antigen-specific responses are qualitatively similar to TT/BT patients, some HHC can respond similarly to BL/LL patients.

The +3187A/G HLA‐G polymorphic site is associated with polar forms and reactive reaction in leprosy

“…This has been confirmed by the observation that polymorphisms of key cytokines genes, such as TNF (Santos et al 2002; Sapkota et al, 2010; Cardoso et al 2011), IL-12 (Alvarado-Navarro et al 2008), IL-4 (Yang et al 2011; Sampaio et al 2012), IL-10, TGF-B, IL-6, and their respective receptors (Aggarwal et al 2011) have been associated with susceptibility to and severity of leprosy.…”

The potential for vaccination in leprosy elimination: new tools for targeted interventions

“…Recently, we observed that these same antigens promote interleukin (IL)-4 or IL-5 secretion in whole blood assays using lepromatous patient blood. Furthermore, we identified an HHC who responded similarly to MB patients (Sampaio et al 2011a) (Fig. 1C), although it remains unclear whether this individual is developing clinical signs.…”

“…Detection of a cellmediated response against Mycobacterium tuberculosis (Mtb) antigens is the preferred evidence for diagnosis of tuberculosis, either through intradermal injection of purified protein derivative testing or more recently, by ex vivo recall (QuantiFERON tests, Cellestis, Melbourne, Australia) (Mazurek & Villarino 2003, Connell et al 2006). We and others have identified various M. leprae antigens that elicit interferon (IFN)-γ secretion from T-cells of tuberculoid leprosy patients, but do not cross react with cells from individuals exposed to BCG or Mtb (Spencer et al 2005, Duthie et al 2008, Geluk et al 2008, 2011, Sampaio et al 2011a. The majority of healthy household contacts (HHC) of MB patients respond in a manner quantitatively and qualitatively comparable to PB patients; however, this is likely indicative of exposure or asymptomatic infection and is a poor diagnostic method for PB disease.…”

“…The ML flow test (KIT Biomedical Research, Royal Tropical Institute, Amsterdam, Netherlands) was developed to analyse blood and serum samples; however, this test has not been widely implemented in field situations and has mainly been used in support of clinical examination as a means to direct the treatment of PB and MB patients , 2009, Contin et al 2011. Sampaio et al (2011a)]. Blood was incubated with recombinant ML0405 protein and cytokines secreted into the plasma analyzed.…”

Prevention of Recurrent Preterm Birth: Role of the Neonatal Follow-up Program

“…Utah residents who are graduates of a NICU and who meet any the following criteria are eligible for enrollment: 1) birth weight ≤1250 grams, 2) gestational age of ≤ 26 weeks, 3) hypoxic ischemic encephalopathy 10 , 4) extracorporeal membrane oxygenation (ECMO). UDOH data suggest that approximately 50% of eligible preterm infants born in the State of Utah are seen in the Utah NFP (unpublished data).…”