Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients

Silva-Freitas, Maria Luciana; Corrêa-Castro, Gabriela; Cota, Gláucia; Giacoia-Gripp, Carmem Beatriz Wagner; Rabello, Ana; Dutra, Juliana Teixeira; Vasconcelos, Zilton Farias Meira de; Savino, Wilson; Da‐Cruz, Alda Maria; Santos-Oliveira, Joanna Reis

doi:10.3389/fimmu.2020.00953

Cited by 16 publications

(17 citation statements)

References 54 publications

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“…In addition to bone marrow failure, reduced thymic output might also play a role in the low number of CD4 + T cells, and indeed, a recent study showed a clear correlation between decreased numbers of recent thymic emigrants and poor CD4+ T cell recovery in HIV patients (48). The study by Silva-Freitas et al also suggested that in VL/HIV co-infected patients who do not relapse, more new emigrant T cells can be detected that might contribute to the control of parasite replication (49). In addition to its potential contribution to the low levels of IFNγ produced in the WBA, a poor CD4 + T cell recovery is also associated with persistent immune activation and inflammation (50); that in turn contribute to higher risks of several morbidities, as well as death (51,52).…”

Section: Discussionmentioning

confidence: 96%

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

Takele

Mulaw

Adem

et al. 2021

Preprint

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Visceral leishmaniasis (VL) has emerged as a clinically important opportunistic infection in HIV patients, as VL/HIV co-infected patients suffer from frequent VL relapse. Here, we followed cohorts of VL patients with or without HIV co-infections in Ethiopia and collected detailed clinical and immunological data during 12 months of follow-up. By the end of the study 78.1% of VL/HIV patients, but none of the VL only patients, had relapsed. Despite clinically defined cure, VL/HIV patients maintained high parasite loads, low BMI, hepatosplenomegaly and pancytopenia throughout follow-up. During detailed immunological study throughout the follow-up period, we identified three markers associated with VL relapse: i) failure to restore antigen-specific production of IFNγ, ii) persistently low CD4+ T cell counts, and iii) high expression of PD1 on CD4+ T cells. We show that these three markers combine well in predicting VL relapse, and that all three measurements are needed for optimal predictive power. These three immunological markers can be measured in primary hospital settings in Ethiopia and can predict VL relapse after anti-leishmanial therapy. The use of our prediction model has the potential to improve disease management and patient care.

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Section: Discussionmentioning

confidence: 96%

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

Takele

Mulaw

Adem

et al. 2021

Preprint

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“…Indeed, the thymus of patients living with HIV presents alterations in the lymphoid and stromal compartments as well as in the generation of the V-beta repertoire of T lymphocytes ( 183 ) that are typical of aging. In addition, HIV infection potentially contributes for the inflammatory immunopathogenesis of VL and, at the same time, impairs the effector immune responses to antigens, including Leishmania ( 184 ).…”

Section: Leishmaniasismentioning

confidence: 99%

Inflammaging in Endemic Areas for Infectious Diseases

et al. 2020

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Immunosenescence is marked by a systemic process named inflammaging along with a series of defects in the immunological activity that results in poor responses to infectious agents and to vaccination. Inflammaging, a state of low-grade chronic inflammation, usually leads to chronic inflammatory diseases and frailty in the elderly. However, some elderly escape from frailty and reach advanced age free of the consequences of inflammaging. This process has been called immunological remodeling, and it is the hallmark of healthy aging as described in the studies of centenarians in Italy. The biological markers of healthy aging are still a matter of debate, and the studies on the topic have focused on inflammatory versus remodeling processes and molecules. The sub-clinical inflammatory status associated with aging might be a deleterious event for populations living in countries where chronic infectious diseases are not prevalent. Nevertheless, in other parts of the world where they are, two possibilities may occur. Inflammatory responses may have a protective effect against these infectious agents. At the same time, the long-term consequences of protective immune responses during chronic infections may result in accelerated immunosenescence in these individuals. Therefore, the biological markers of healthy aging can vary according to environmental, cultural, and geographical settings that reflect worldwide, and in a non-biased, non-westernized perspective, the changes that we experience regarding our contacts with microorganisms and the outcomes of such contacts.

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“…Similar results were observed in VL/HIV coinfection [23]. This de cit in the recovery of CD4 + T lymphocytes can be related to an impaired input of cells originated from bone marrow, de cient replication rate or thymic dysfunction [24,[36][37]. Low CD4 + T cell counts in VL/HIV coinfected patients during the active phase of VL was a predictor of a poor prognosis: death or recurrence [38][39].…”

Section: Discussionmentioning

confidence: 53%

High Levels of anti-Leishmania IgG3 and Low CD4+ T Cells Count were Associated with Relapses in Visceral Leishmaniasis

Kuschnir

Pereira

Dutra

et al. 2020

Preprint

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Background: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4+ T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1β), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4-5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL.Methods: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n=5) and non-relapsing (NR-VL, n=10) and evaluated during active disease, immediately after treatment (post-treatment) and six months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4+ and CD8+ T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls.Results: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p<0.05), a profile reversed during the post-treatment phase. All patients had low CD4+ T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p<0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p<0.05). In addition, IgG3 levels were negatively correlated with CD4+ T counts in the R-VL group (r=-0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity. Conclusions: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.

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Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients

Cited by 16 publications

References 54 publications

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

Inflammaging in Endemic Areas for Infectious Diseases

High Levels of anti-Leishmania IgG3 and Low CD4+ T Cells Count were Associated with Relapses in Visceral Leishmaniasis

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