Revealing a Novel Antigen Repressor of Differentiation Kinase 2 for Diagnosis of Human Visceral Leishmaniasis in India

Abstract

Visceral leishmaniasis (VL) is one of the major global health concerns due to its association with morbidity and mortality. All available diagnostic tools have been, until now, unable to provide a very specific and cost-effective mode of detection for VL globally. Therefore, the design of robust, specific, and commercially translatable diagnostic tests is urgently required. Currently, we are attempting to identify and explore the diagnostic potential of a novel parasite antigen. Repressor of differentiation kinase 2 (RDK2), a serine/threonine kinase, has a versatile role in parasite life cycle progression. However, its role as a diagnostic candidate for VL has not been investigated. Herein, we cloned and over-expressed LdRDK2 and studied the recombinant RDK2 for the diagnosis of human VL using serum and urine samples. In silico analysis predicted that RDK2 is conserved among Leishmania species with the least conservation in humans. RDK2 developed immune-reactive bands with antibodies present in VL patients’ sera, and it demonstrated no cross-reactivity with sera from healthy controls and other diseases. Additionally, RDK2 antigen demonstrated a significant reactivity with IgG antibodies of VL patients’ sera, with 78% sensitivity and 86.67% specificity as compared to healthy controls and other diseases. Furthermore, we evaluated its utility for non-invasive diagnosis of VL using patients’ urine samples and found 93.8% sensitivity and 85.7% specificity. RDK2 was found to have better sensitivity and treatment response in patients’ urine compared to serum samples, indicating its role as a promising point of care (POC) antigen. In a nutshell, we explored the role of RDK2 as a potential diagnostic marker for VL in both invasive and non-invasive modes as well as its utility as a promising POC antigen for treatment response cases.

The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective

“…However, there have been geographical differences in PMM efficacy against VL between East Africa and India ( Hailu et al., 2010 ; Musa et al., 2010 ). Finally, due to severe toxicity, pentamidine (PTD) has been discontinued for the treatment of VL and is now only used in the treatment of CL in South America ( Soto et al., 1994 ; Lai a Fat et al., 2002 ; Roussel et al., 2006 ; Bhattacharyya et al., 2022 ). The mode of action of antimonials is unknown despite its use for more than six decades.…”

Cellular landscaping of cisplatin resistance in cervical cancer

“…The risk factors that might cause or worsen the occurrence of CC are polymorphic genes, intercourse with many different partners, lamin A/C deficit, and smoking. The significance of this virus is underscored by its capacity to cause 5% of all human malignancies through HPV encoded oncoproteins (E5, E6, and E7) as key players in viral pathogenesis [3,4]. Despite being the canonical therapy, chemotherapy is deemed ineffective owing to the developing drug resistance [5].…”