scholarly journals How immunodeficiency can lead to malignancy

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 287-295
Author(s):  
Sung-Yun Pai ◽  
Kathryn Lurain ◽  
Robert Yarchoan
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
B Lymphocyte ◽  
Killer Cell ◽  
Kaposi Sarcoma ◽  
People Living With Hiv ◽  
Oncogenic Viruses ◽  
Inborn Errors ◽  
Increased Risk ◽  
T Cell Lymphopenia

Abstract Immunodeficiency, whether acquired in the case of human immunodeficiency virus (HIV) infection or congenital due to inborn errors of immunity (IEIs), presents clinically with not only infection and immune dysregulation but also increased risk of malignancy. The range of malignancies seen is relatively limited and attributable to the particular cellular and molecular defects in each disease. CD4+ T-cell lymphopenia in people living with HIV infection (PLWH) and certain IEIs drive the predisposition to aggressive B-cell non-Hodgkin lymphomas, including certain rare subtypes rarely seen in immunocompetent individuals. PLWH and IEI that lead to profound T-cell lymphopenia or dysfunction also are at risk of cancers related to oncogenic viruses such as Kaposi sarcoma herpesvirus, Epstein-Barr virus, human papillomavirus (HPV), and Merkel cell polyomavirus. IEIs that affect natural killer cell development and/or function heavily predispose to HPV-associated epithelial cancers. Defects in DNA repair pathways compromise T- and B-lymphocyte development during immune receptor rearrangement in addition to affecting hematopoietic and epithelial DNA damage responses, resulting in both hematologic and nonhematologic cancers. Treatment of cancers in immunodeficient individuals should be curative in intent and pursued in close consultation with disease experts in immunology and infectious disease.

scholarly journals HIV infection alters SARS-CoV-2 responsive immune parameters but not clinical outcomes in COVID-19 disease

2020 ◽  
Author(s):  
Farina Karim ◽  
Inbal Gazy ◽  
Sandile Cele ◽  
Yenzekile Zungu ◽  
Robert Krause ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Hiv Infection ◽  
Disease Severity ◽  
Immune Cell ◽  
Killer Cell ◽  
People Living With Hiv ◽  
Antibody Secreting Cell ◽  
The Impact ◽  
Hiv Negative

AbstractHIV infection alters the immune response and can compromise protective immunity to multiple pathogens following vaccination. We investigated the impact of HIV on the immune response to SARS-CoV-2 using longitudinal samples from 124 participants from KwaZulu-Natal, South Africa, an area of extremely high HIV prevalence. 44% of participants were people living with HIV (PLWH) and commonly had other co-morbidities, including obesity, hypertension, and diabetes. The majority of PLWH but not HIV negative participants showed CD8 T cell expansion above the normal range post-SARS-CoV-2. Yet, in participants with HIV suppressed by antiretroviral therapy (ART), CD8 expansion was associated with milder COVID-19 disease. There were multiple differences in T cell, B cell, and natural killer cell correlations in PLWH compared to HIV negative participants, including lower tissue homing CXCR3+ CD8 T cells in the presence of SARS-CoV-2 RNA in PLWH but not HIV negative and a pronounced early antibody secreting cell (ASC) expansion in HIV negative but not PLWH. These changes were COVID-19 associated: low CXCR3 correlated with increased COVID-19 disease severity across groups, and high ASC correlated with increased disease severity in HIV negative participants and waned when SARS-CoV-2 was cleared. Despite the altered response of immune cell subsets, COVID-19 disease in PLWH was mostly mild and similar to HIV negative participants. This likely reflects the heterogeneity of an effective COVID-19 immune response. Whether the differences in immune cell dynamics in PLWH will lead to different long-term consequences or compromise vaccination is yet to be determined.

scholarly journals WT1 Tumor Antigen is Overexpressed in Kaposi Sarcoma and is Regulated by KSHV vFLIP

2021 ◽  
Author(s):  
Ayana Morales ◽  
Caitlyn Genovese ◽  
Matthew Bott ◽  
Julio Alvarez ◽  
Sung Soo Mun ◽  
...  
Keyword(s):  
T Cell ◽  
Therapeutic Approach ◽  
Poor Prognosis ◽  
Wilms Tumor ◽  
Kaposi Sarcoma ◽  
Host Protein ◽  
People Living With Hiv ◽  
Potential Biomarker ◽  
Wilms Tumor 1

AbstractPurposeWilms’ tumor 1 (WT1) is overexpressed in several cancers, and WT1 expression levels are associated with poor prognosis. As a host protein that functions as an oncogene, it represents an important immunotherapeutic target. This study evaluated WT1 expression in Kaposi sarcoma (KS) tumors to assess whether immunotherapy targeting WT1 is a potential therapeutic approach for KS. We also investigated the role of the causal agent of KS, Kaposi sarcoma herpesvirus (KSHV/HHV-8) in regulating WT1 expression.Experimental designImmunohistochemistry for WT1, KSHV, and B and T cells subsets, followed by image analysis, was performed in 363 KS tumor biopsies. Expression of KSHV vFLIP was evaluated by immunofluorescence. Primary endothelial cell cultures and cell lines were infected with KSHV in vitro, or transduced with an inducible vFLIP vector and induced with doxycycline, and then assessed for WT1 expression. Binding of ESK-1, a T cell receptor mimic therapeutic antibody that recognizes WT1 peptides presented on MHC HLA-A0201, was assessed using flow cytometry.ResultsWe report overexpression of WT1 in KS tumors, which was associated with increased with increasing histopathologic stage and the proportion of KSHV-infected cells. Areas with high WT1 expression showed sparse T cell infiltrates. KSHV infection in vitro resulted in WT1 upregulation, mediated by the viral protein vFLIP, which resulted in stronger binding of ESK1.ConclusionsKS lesions express high levels of WT1, a process regulated by the KSHV-encoded vFLIP. These findings suggest that immunotherapy directed against WT1 may represent a therapeutic approach for this cancer.Translational RelevanceKaposi sarcoma (KS) is a vascular neoplasm caused by the Kaposi sarcoma herpesvirus (KSHV/HHV-8). People living with HIV are not only at a significantly higher risk of developing KS, but also often have a more aggressive clinical course. Although antiretroviral therapy may cause regression of HIV-associated KS lesions, advanced cases of KS also require chemotherapy, which is rarely curative. Wilms’ tumor 1 (WT1) has been reported to be overexpressed in various cancers, functioning as an oncogene and associated with a poor prognosis. WT1 is also an important immunotherapeutic target, with several WT1-directed therapies showing promising results in early clinical trials for leukemias and solid tumors. Here we report high expression of WT1 in KS, especially in higher histological stages. Our findings provide pre-clinical evidence that supports conducting anti-WT1 immunotherapy trials in KS, and evaluating WT1 expression as a potential biomarker to identify individuals most likely to benefit.

scholarly journals COVID-19 Vaccination in People Living with HIV (PLWH) in China: A Cross Sectional Study of Vaccine Hesitancy, Safety, and Immunogenicity

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1458
Author(s):  
Ying Liu ◽  
Junyan Han ◽  
Xin Li ◽  
Danying Chen ◽  
Xuesen Zhao ◽  
...  
Keyword(s):  
T Cell ◽  
Negative Impact ◽  
Immunological Response ◽  
Cd4 T Cell ◽  
Vaccine Hesitancy ◽  
People Living With Hiv ◽  
Cross Sectional ◽  
Cell Counts ◽  
Increased Risk ◽  
Living With Hiv

The administration of COVID-19 vaccines is the primary strategy used to prevent further infections by COVID-19, especially in people living with HIV (PLWH), who are at increased risk for severe symptoms and mortality. However, the vaccine hesitancy, safety, and immunogenicity of COVID-19 vaccines among PLWH have not been fully characterized. We estimated vaccine hesitancy and status of COVID-19 vaccination in Chinese PLWH, explored the safety and impact on antiviral therapy (ART) efficacy and compared the immunogenicity of an inactivated vaccine between PLWH and healthy controls (HC). In total, 27.5% (104/378) of PLWH hesitated to take the vaccine. The barriers included concerns about safety and efficacy, and physician counselling might help patients overcome this vaccine hesitancy. A COVID-19 vaccination did not cause severe side effects and had no negative impact on CD4+ T cell counts and HIV RNA viral load. Comparable spike receptor binding domain IgG titer were elicited in PLWH and HC after a second dose of the CoronaVac vaccine, but antibody responses were lower in poor immunological responders (CD4+ T cell counts < 350 cells/µL) compared with immunological responders (CD4+ T cell counts ≥ 350 cells/µL). These data showed that PLWH have comparable safety and immune response following inactivated COVID-19 vaccination compared with HC, but the poor immunological response in PLWH is associated with impaired humoral response.

scholarly journals Factor V is an immune inhibitor that is expressed at increased levels in leukocytes of patients with severe Covid-19

2021 ◽  
Author(s):  
Jun Wang ◽  
Prasanti Kotagiri ◽  
Paul A Lyons ◽  
Federica Mescia ◽  
Laura Bergamaschi ◽  
...  
Keyword(s):  
T Cell ◽  
T Regulatory Cells ◽  
Adaptive Immune System ◽  
Factor V ◽  
Adaptive Immune ◽  
Thrombin Cleavage ◽  
Increased Risk ◽  
Plasma Factor ◽  
T Cell Lymphopenia

AbstractSevere Covid-19 is associated with elevated plasma Factor V (FV) and increased risk of thromboembolism. We report that neutrophils, T regulatory cells (Tregs), and monocytes from patients with severe Covid-19 express FV, and expression correlates with T cell lymphopenia. In vitro full length FV, but not FV activated by thrombin cleavage, suppresses T cell proliferation. Increased and prolonged FV expression by cells of the innate and adaptive immune systems may contribute to lymphopenia in severe Covid-19. Activation by thrombin destroys the immunosuppressive properties of FV. Anticoagulation in Covid-19 patients may have the unintended consequence of suppressing the adaptive immune system.

scholarly journals Echocardiographic Assessment of Asymptomatic US Air Force Members with Early HIV Infection

2019 ◽  
Author(s):  
Gadiel Rafael Alvarado ◽  
Courtney Usry ◽  
Rosco Gore ◽  
James Watts ◽  
Jason Okulicz
Keyword(s):  
Hiv Infection ◽  
Air Force ◽  
Global Longitudinal Strain ◽  
People Living With Hiv ◽  
Hiv Diagnosis ◽  
Cvd Risk ◽  
Us Air Force ◽  
Increased Risk ◽  
Hiv Acquisition ◽  
Living With Hiv

Abstract Objective People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD) and development of subclinical echocardiographic abnormalities. The pathogenicity of HIV induced cardiotoxicity has been described however the time to development of echocardiographic abnormalities after HIV acquisition remains unclear. In this study we describe the echocardiographic evaluations of asymptomatic US Air Force members who were diagnosed with HIV infection. Results Patients (n=50) were predominantly male (96%), mostly black (60%), with a mean age of 28 years. At HIV diagnosis, the mean viral load was 112,585 copies/mL and CD4 count was 551 cells/uL; 2 patients were diagnosed with AIDS. All were found to have normal systolic ejection fraction (EF) and global longitudinal strain (GLS) however evidence of right ventricular dilatation and cardiac remodeling was observed in 7 (14%) and 13 (26%) patients, respectively. Subgroup analyses showed no significant differences in echocardiographic findings by HIV disease severity or CVD risk factors (p >0.05 for all). This study suggests that untreated HIV may have a low impact on the development of echocardiographic abnormalities shortly after seroconversion. Longitudinal studies are warranted to determine the optimal CVD risk assessment strategies for PLHIV.

scholarly journals Risk of adverse COVID-19 outcomes for people living with HIV: a rapid review and meta-analysis

2020 ◽  
Author(s):  
Maya Mellor ◽  
Anne Bast ◽  
Nicholas Jones ◽  
Nia Roberts ◽  
Jose Ordonez-Mena ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Meta Analysis ◽  
Cd4 T Cell ◽  
Rapid Review ◽  
People Living With Hiv ◽  
Hiv Viral Load ◽  
Increased Risk ◽  
Living With Hiv ◽  
Cd4 T Cell Count

Objective: To assess whether people living with HIV (PLWH) are at increased risk of COVID-19 mortality or adverse outcomes, and whether antiretroviral therapy (ART) influences this risk. Design: Rapid review with meta-analysis and narrative synthesis. Methods: We searched databases including Embase, Medline, medRxiv, and Google Scholar up to 26th August 2020 for studies describing COVID-19 outcomes in PLWH and conducted a meta-analysis of higher quality studies. Results: We identified 1,908 studies and included 19 in the review. In a meta-analysis of five studies, PLWH had a higher risk of COVID-19 mortality (hazard ratio (HR) 1.93, 95% Confidence Interval (CI): 1.59-2.34) compared to people without HIV. Risk of death remained elevated for PLWH in a subgroup analysis of hospitalised cohorts (HR 1.54, 95% CI: 1.05-2.24) and studies of PLWH across all settings (HR 2.08, 95%CI: 1.69-2.56). Eight other studies assessed the association between HIV and COVID-19 outcomes, but provided inconclusive, lower-quality evidence due to potential confounding and selection bias. There were insufficient data on the effect of CD4+ T cell count and HIV viral load on COVID-19 outcomes. Eleven studies reported COVID-19 outcomes by ART-regimen. In the two largest studies, tenofovir-disoproxil-fumarate (TDF)-based regimens were associated with a lower risk of adverse COVID-19 outcomes, although these analyses are susceptible to confounding by comorbidities. Conclusion: Evidence is emerging that suggests a moderately increased risk of COVID-19 mortality amongst PLWH. Further investigation into the relationship between COVID-19 outcomes and CD4+ T cell count, HIV viral load, ART and the use of TDF is warranted.

scholarly journals Echocardiographic Assessment of Asymptomatic US Air Force Members with Early HIV Infection

2019 ◽  
Author(s):  
Gadiel Rafael Alvarado ◽  
Courtney Usry ◽  
Rosco Gore ◽  
James Watts ◽  
Jason Okulicz
Keyword(s):  
Hiv Infection ◽  
Air Force ◽  
Ventricular Remodeling ◽  
Medical Center ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Us Air Force ◽  
Increased Risk

Abstract Objective People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD) and development of subclinical echocardiographic abnormalities. However, there is scant evidence of the echocardiographic changes that occur shortly after seroconversion. In this study we describe the echocardiographic evaluations of asymptomatic US Air Force members who were diagnosed with HIV infection and evaluated at the San Antonio Military Medical Center between September 1, 2015 and September 30, 2016. Results Patients (n=50) were predominantly male (96%), mostly African American (60%), with a mean age of 28 years. At HIV diagnosis, the mean viral load was 112,585 copies/mL and CD4 count was 551 cells/uL. All were found to have normal left ventricular systolic ejection fraction (EF) and global longitudinal strain (GLS) however evidence of right ventricular dilatation and left ventricular remodeling was observed in 7 (14%) and 13 (26%) patients, respectively. Subgroup analyses showed no significant differences in echocardiographic findings by HIV disease severity or CVD risk factors (p >0.05 for all).This study suggests that untreated HIV may have a low impact on the development of echocardiographic abnormalities shortly after seroconversion. Longitudinal studies are warranted to determine the optimal CVD risk assessment strategies for PLHIV.

scholarly journals Echocardiographic assessment of asymptomatic US Air Force members with early HIV infection

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Gadiel R. Alvarado ◽  
Courtney R. Usry ◽  
Rosco S. Gore ◽  
James A. Watts ◽  
Jason F. Okulicz
Keyword(s):  
Hiv Infection ◽  
Air Force ◽  
Ventricular Remodeling ◽  
Medical Center ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Us Air Force ◽  
Increased Risk

Abstract Objective People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD) and development of subclinical echocardiographic abnormalities. However, there is scant evidence of the echocardiographic changes that occur shortly after seroconversion. In this study we describe the echocardiographic evaluations of asymptomatic US Air Force members who were diagnosed with HIV infection and evaluated at the San Antonio Military Medical Center between September 1, 2015 and September 30, 2016. Results Patients (n = 50) were predominantly male (96%), mostly African American (60%), with a mean age of 28 years. At HIV diagnosis, the mean viral load was 112,585 copies/mL and CD4 count was 551 cells/μL. All were found to have normal left ventricular systolic ejection fraction (EF) and global longitudinal strain (GLS) however evidence of right ventricular dilatation and left ventricular remodeling was observed in 7 (14%) and 13 (26%) patients, respectively. Subgroup analyses showed no significant differences in echocardiographic findings by HIV disease severity or CVD risk factors (p > 0.05 for all).This study suggests that untreated HIV may have a low impact on the development of echocardiographic abnormalities shortly after seroconversion. Longitudinal studies are warranted to determine the optimal CVD risk assessment strategies for PLHIV.

scholarly journals HIV modulates the expression of ligands important in triggering natural killer cell cytotoxic responses on infected primary T-cell blasts

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1207-1214 ◽  
Author(s):  
Jeffrey Ward ◽  
Matthew Bonaparte ◽  
Jennifer Sacks ◽  
Jacqueline Guterman ◽  
Manuela Fogli ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Target Cells ◽  
Nk Cell Receptors ◽  
Infected Cells ◽  
Cytotoxic Responses

AbstractThe ability of natural killer (NK) cells to kill virus-infected cells depends on the presence of ligands for activation receptors on the target cells. We found the presence of few, if any, NKp30 and NK46 ligands on T cell blasts infected with HIV, although NKp44 ligands were found on infected cells. HIV does induce the NKG2D ligands ULBP-1, -2, and -3. These ligands are involved in triggering NK cells to kill autologous HIV-infected cells, because interfering with the interaction between NKG2D, but not NKp46, on NK cells and its ligands on HIV-infected cells drastically reduced the lysis of infected cells. Interfering with the binding of the NK-cell coreceptors NTB-A and 2B4 to their ligands also decreased destruction by NK cells. The coreceptor ligands, NTB-A and CD48, were also found to be down-regulated during the course of HIV infection. Thus, ligands for NK-cell receptors are modulated during the course of HIV infection, which may greatly alter NK cells' ability to kill the infected cells.

scholarly journals Glycoprotein Profile Assessed by 1H-NMR as a Global Inflammation Marker in Patients with HIV Infection. A Prospective Study

2020 ◽  
Vol 9 (5) ◽  
pp. 1344
Author(s):  
Ana-Irene Malo ◽  
Anna Rull ◽  
Josefa Girona ◽  
Pere Domingo ◽  
Rocío Fuertes-Martín ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
1H Nmr ◽  
Clinical Status ◽  
Cell Number ◽  
Cd4 T Cell ◽  
People Living With Hiv ◽  
Clinical Value ◽  
Aggregation State ◽  
A Prospective Study

Plasma glycoproteins are a composite biomarker of inflammation and can be detected by 1H-NMR. The aim of this study was to prospectively appraise the clinical value of plasma glycoproteins assessed by 1H-NMR in people living with HIV (PLWH). A total of 221 patients with HIV infection were recruited and studied at baseline and at 48 and 144 weeks. Patients were distributed into two groups according to baseline CD4+ T-cell number below or above 200 cells/µL. Patients with fewer than 200 cells/µL were distributed into the responders and nonresponders according to antiretroviral therapy (ART) response at 144 weeks. Glycoprotein concentrations were determined by 1H-NMR arising from the protein bond N-acetylglucosamine and N-acetylgalactosamine signals (GlycA); and N-acetylneuraminic acid signal (GlycB) associated with the sugar–protein bond concentration and aggregation state (shapes (height/width)). Basal glycoprotein concentrations were higher in patients with < 200 CD4+ T-cell/μL (Glyc A: 1040(917.9–1199.1) vs. 950.4(845.5–1050.9), p < 0.001, and Glyc B: 521(440.3–610.3) vs. 468.6(417.9–507.0) μ mol/L, p < 0.001) being reduced by ART. The height/width (H/W) ratio was the parameter showing a better association with this clinical status. Baseline glycoproteins predict the condition of responder/nonresponder. In this study, 1H-NMR glycoproteins provide novel insights to assess inflammation status and have prognostic value in PLWH.

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