Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

Vijayamahantesh,; Amit, Ajay; Dikhit, Manas Ranjan; Pandey, R. K.; Singh, Kuljit; Mishra, Ritesh; Das, Vidya Nand Rabi; Das, Pradeep; Bimal, Sanjiva

doi:10.1371/journal.pone.0154117

Cited by 16 publications

(14 citation statements)

References 42 publications

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“…ADA might be increased in an attempt to maintain the clearance of the high levels of adenosine produced by a persistent inflammatory microenvironment and the increased activity of ecto‐nucleotidases . Several studies have shown the clinical use of ADA levels as a diagnostic and/or prognostic marker in various diseases with an important inflammatory component such as oral squamous cell carcinoma, chronic lymphocytic leukemia, tuberculosis, common chronic ears, nose and throat infections, Chagas disease, and leishmaniasis . The great difference in ADA levels between ovarian endometriomas and simple cysts found here suggests that ADA can also be a good biomarker for endometriosis.…”

Section: Discussionmentioning

confidence: 74%

Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of ovarian endometriomas as candidate biomarkers of endometriosis

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Fernández-Montolí

et al. 2017

American J Rep Immunol

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Section: Discussionmentioning

confidence: 74%

Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of ovarian endometriomas as candidate biomarkers of endometriosis

Trapero

Jover

Fernández-Montolí

et al. 2017

American J Rep Immunol

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“…Despite the IL-10 inducing property of P3, the same peptide was also found to be an IFN-γ inducer against other cytokines. It is well known that the fate of the disease mainly relies on the Th1 versus Th2 cytokine balance ( 69 , 70 ) and the clinical cure is deeply associated with sustained elevated IFN-γ and downregulated IL-10 levels ( 70 ). All of this information suggests that these optimal set of epitopes with the exception of P3 are possibly highly immunogenic with the added advantages of exhibiting a HLA cross-presentation ability.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential MHC Class-II-Restricted Epitopes Derived from Leishmania donovani Antigens by Reverse Vaccinology and Evaluation of Their CD4+ T-Cell Responsiveness against Visceral Leishmaniasis

et al. 2017

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Visceral leishmaniasis (VL) is one of the most neglected tropical diseases for which no vaccine exists. In spite of extensive efforts, no successful vaccine is available against this dreadful infectious disease. To support vaccine development, an immunoinformatics approach was applied to screen potential MHC class-II-restricted epitopes that can activate the immune cells. Initially, 37 epitopes derived from six stage-dependent, overexpressed antigens were predicted, which were presented by at least 26 diverse MHC class-II allele. Based on a population coverage analysis and human leukocyte antigen cross-presentation ability, six of the 37 epitopes were selected for further analysis. Stimulation with synthetic peptide alone or as a cocktail triggered intracellular IFN-γ production. Moreover, specific IgG antibodies were detected in the serum of active VL cases against P1, P4, P5, and P6 in order to evaluate the peptide effect on the humoral immune response. Additionally, most of the peptides, except P2, were found to be non-inducers of CD4+ IL-10 against both active VL as well as treated VL subjects. This finding suggests there is no role of these peptides in the pathogenesis of Leishmania. Peptide immunogenicity was validated in BALB/c mice immunized with a cocktail of synthetic peptide emulsified in complete Freund’s adjuvant/incomplete Freund’s adjuvant. The immunized splenocytes induced strong spleen cell proliferation upon parasite re-stimulation. Furthermore, increased IFN-γ, interleukin-12, IL-17, and IL-22 production augmented with elevated nitric oxide (NO) synthesis is thought to play a crucial role in macrophage activation. In this investigation, we identified six MHC class-II-restricted epitope hotspots of Leishmania antigens that induce CD4+ Th1 and Th17 responses, which could be used to potentiate a human universal T-epitope vaccine against VL.

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“…Recently, serum adenosine deaminase (ADA) levels were found to be raised in PKDL and decreased during treatment [ 53 ].…”

Section: Clinical Features and Diagnosismentioning

confidence: 99%

Post-kala-azar dermal leishmaniasis in the Indian subcontinent: A threat to the South-East Asia Region Kala-azar Elimination Programme.

et al. 2017

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BackgroundThe South-East Asia Region Kala-azar Elimination Programme (KAEP) is expected to enter the consolidation phase in 2017, which focuses on case detection, vector control, and identifying potential sources of infection. Post-kala-azar dermal leishmaniasis (PKDL) is thought to play a role in the recurrence of visceral leishmaniasis (VL)/kala-azar outbreaks, and control of PKDL is among the priorities of the KAEP.Methodology and principal findingWe reviewed the literature with regard to PKDL in Asia and interpreted the findings in relation to current intervention methods in the KAEP in order to make recommendations. There is a considerable knowledge gap regarding the pathophysiology of VL and PKDL, especially the underlying immune responses. Risk factors (of which previous VL treatments may be most important) are poorly understood and need to be better defined. The role of PKDL patients in transmission is largely unknown, and there is insufficient information about the importance of duration, distribution and severity of the rash, time of onset, and self-healing. Current intervention methods focus on active case detection and treatment of all PKDL cases with miltefosine while there is increasing drug resistance. The prevention of PKDL by improved VL treatment currently receives insufficient attention.Conclusion and significancePKDL is a heterogeneous and dynamic condition, and patients differ with regard to time of onset after VL, chronicity, and distribution and appearance of the rash, as well as immune responses (including tendency to self-heal), all of which may vary over time. It is essential to fully describe the pathophysiology in order to make informed decisions on the most cost-effective approach. Emphasis should be on early detection of those who contribute to transmission and those who are in need of treatment, for whom short-course, effective, and safe drug regimens should be available. The prevention of PKDL should be emphasised by innovative and improved treatment for VL, which may include immunomodulation.

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Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

Cited by 16 publications

References 42 publications

Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of ovarian endometriomas as candidate biomarkers of endometriosis

Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of ovarian endometriomas as candidate biomarkers of endometriosis

Identification of Potential MHC Class-II-Restricted Epitopes Derived from Leishmania donovani Antigens by Reverse Vaccinology and Evaluation of Their CD4+ T-Cell Responsiveness against Visceral Leishmaniasis

Post-kala-azar dermal leishmaniasis in the Indian subcontinent: A threat to the South-East Asia Region Kala-azar Elimination Programme.

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