Serum Levels of Soluble CD40 Ligand and Neopterin in HIV Coinfected Asymptomatic and Symptomatic Visceral Leishmaniasis Patients

Abstract

Human Immunodeficiency Virus (HIV) co-infection drastically increases the risk of developing overt visceral leishmaniasis (VL). The asymptomatic Leishmania infection window constitutes an opportunity to identify those HIV patients at highest risk by defining early markers associated with disease susceptibility or resistance. As intracellular parasite killing is essential, we investigated whether serum markers of macrophage activation were notably affected in HIV patients with an asymptomatic Leishmania infection or overt visceral leishmaniasis disease. Serum levels of soluble CD40 ligand and neopterin were assessed in 24 active VL-HIV patients, 35 HIV patients with asymptomatic Leishmania infection and 35 HIV endemic controls. All patients were recruited in L. donovani endemic regions of North-West Ethiopia. The serum levels of sCD40L and neopterin significantly decreased and increased in HIV patients with active VL compared to HIV patients with asymptomatic Leishmania infection, respectively. No statistically significant differences could be detected in neopterin and sCD40L levels between Leishmania asymptomatically infected HIV patients and endemic HIV control patients. However, an inverse trend, between Leishmania antibody positivity or VL development and neopterin levels could be seen. The CD4+ T-cell count was inversely correlated with serum neopterin levels, but not with sCD40L levels. Our results in HIV coinfected patients, correspond with the postulated protective role of sCD40L in VL and underline the importance of the CD40-CD40L pathway in resistance against the parasite. Neopterin levels suggest an increased macrophage activation upon infection and could have a value in clinical algorithms to, although non-specifically, improve prediction of VL development in HIV patients with asymptomatic Leishmania infection.

Recurrent visceral leishmaniasis relapses in HIV co-infected patients are characterized by less efficient immune responses and higher parasite load

“… 15 In a separate study, it was shown that decreased levels of CD40L and increased levels of neopterin, a molecule associated with activation of macrophages, were present in the plasma of HIV/VL as compared to patients with HIV. 16 Van den Bergh et al. suggested that myeloid-derived suppressor cells might play a role in severely immunocompromised HIV/VL co-infected patients.…”

Altered co-stimulatory and inhibitory receptors on monocyte subsets in patients with visceral leishmaniasis

“…Little is known about CD40 expression on monocytes in VL patients. The levels of the soluble form of its ligand, sCD40L, have been shown to be lower in plasma of HIV/VL patients as compared to patients with HIV asymptomatically co-infected with Leishmania parasites [29]. De Oliveira et al .…”

“…10 non-endemic male controls with no prior history of VL were recruited amongst the staff of the University of Gondar. The median ages of the three cohorts were similar: VL patients at ToD: 25 [20][21][22][23][24][25][26][27][28][29][30]; VL patients at EoT: 23.5 [18.5-26.8] and controls: 24 [20.5-27.3] years old (p=0.7495). Informed written consent was obtained from each patient and control.…”

Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments

“…In further analysis, the sCD40L levels also negatively correlated with the spleen size in the SbV + NAC group, but not in the control SbV group. sCD40L has been previously demonstrated as an important biomarker of VL disease, associated with better outcomes, stimulating resolutive immune response ( Okwor and Uzonna, 2016 ; Adriaensen et al., 2018 ). Previous data of our group, using patients from the same local of this study, demonstrate that sCD40L is an important biomarker in VL, indicating a favorable evolution during and after treatment, negatively correlating with the spleen sizes and parasite load in patients with VL ( de Oliveira et al., 2013 ).…”