RESUMO
Kaposi sarcoma (KS) is an angioproliferative disorder caused by human herpesvirus-8 (HHV-8) infection. KS manifests as vascular and mucosal nodules and is classified into four subtypes based on epidemiology, clinical presentation, histopathology, and HHV-8/human immunodeficiency virus serology. Here, we present a unique case of classic KS in an 84-year-old immunocompetent Haitian male patient, highlighting the rarity of this variant in this population. Additionally, our article delves into the broader context by reviewing a few documented cases of classic KS in the Caribbean region.
RESUMO
Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.
Assuntos
Coinfecção , Infecções por HIV , Herpesvirus Humano 8 , Sarcoma de Kaposi , Produtos do Gene tat do Vírus da Imunodeficiência Humana , Humanos , Sarcoma de Kaposi/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Herpesvirus Humano 8/genética , Feminino , Adulto , Pessoa de Meia-Idade , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Coinfecção/virologia , Coinfecção/tratamento farmacológico , HIV-1/genética , HIV-1/efeitos dos fármacos , Variação Genética , Carga Viral , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4RESUMO
ABSTRACT Background: The 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed. Objectives: To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoid-proliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated. Methods: HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, in situ hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data. Results: We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related. Conclusion: IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.
RESUMO
Background: The 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed. Objectives: To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoidproliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated. Materials and Methods: HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, in situ hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data. Results: We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related. Conclusion: IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.
RESUMO
Kaposi's sarcoma (KS) may derive from Kaposi's sarcoma herpesvirus (KSHV)-infected human mesenchymal stem cells (hMSCs) that migrate to sites characterized by inflammation and angiogenesis, promoting the initiation of KS. By analyzing the RNA sequences of KSHV-infected primary hMSCs, we have identified specific cell subpopulations, mechanisms, and conditions involved in the initial stages of KSHV-induced transformation and reprogramming of hMSCs into KS progenitor cells. Under proangiogenic environmental conditions, KSHV can reprogram hMSCs to exhibit gene expression profiles more similar to KS tumors, activating cell cycle progression, cytokine signaling pathways, endothelial differentiation, and upregulating KSHV oncogenes indicating the involvement of KSHV infection in inducing the mesenchymal-to-endothelial (MEndT) transition of hMSCs. This finding underscores the significance of this condition in facilitating KSHV-induced proliferation and reprogramming of hMSCs towards MEndT and closer to KS gene expression profiles, providing further evidence of these cell subpopulations as precursors of KS cells that thrive in a proangiogenic environment.
Assuntos
Herpesvirus Humano 8 , Células-Tronco Mesenquimais , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/fisiologia , Herpesvirus Humano 8/genética , Sarcoma de Kaposi/virologia , Células-Tronco Mesenquimais/virologia , Diferenciação Celular , Células Cultivadas , Perfilação da Expressão Gênica , Proliferação de CélulasRESUMO
Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV- patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status.
Assuntos
Infecções por HIV , Sarcoma de Kaposi , Sulfonamidas , Humanos , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/metabolismo , Infecções por HIV/metabolismo , Valganciclovir/metabolismo , Valganciclovir/uso terapêutico , Linfócitos T CD4-Positivos/metabolismo , Subpopulações de Linfócitos T , Linfócitos T CD8-Positivos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Carga ViralRESUMO
ABSTRACT We present an interesting case of a 62-year-old black female, presented to the ophthalmological hospital with a little "nevus" on the left eye previously visualized at the mirror, with one month of development. Physical examination with slit lamp (biomicroscopy) showed a group of painless veins, with vascular redness, and a mass nodular aspect in the mid temporal bulbar conjunctiva, of approximately 2mmx4mm.
RESUMO Apresentamos o interessante caso de uma mulher negra de 62 anos, que deu entrada no hospital oftalmológico com um pequeno nevo no olho esquerdo previamente visualizado ao espelho, com 1 mês de evolução. O exame físico com lâmpada de fenda (biomicroscopia) mostrou um grupo de veias indolor e vermelhidão vascular, com uma massa de aspecto nodular na conjuntiva bulbar temporal média, de aproximadamente 2mmx4mm.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/etiologia , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/etiologia , Sarcoma de Kaposi/cirurgia , Infecções por Treponema/diagnóstico , Biópsia , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV , Neoplasias Oculares/cirurgia , Microscopia com Lâmpada de FendaRESUMO
The recommended first-line chemotherapy agents for managing Kaposi sarcoma (KS) in high-income countries are expensive and often unavailable in developing nations such as Peru. Limited data exist on whether management practices in these countries affect patient outcomes. We assessed the real-world treatment approaches and outcomes of patients with KS in Peru. We retrospectively reviewed the medical records of patients with acquired immunodeficiency syndrome-related KS (AIDS-related KS; n = 95) and classic KS (CKS; n = 81) diagnosed at a tertiary center between 2000 and 2014 in Lima, Peru. We used the Kaplan-Meier method to estimate overall survival (OS) rates. The median follow-up was 64 months for AIDS-related KS and 88 months for CKS. The median age of patients with AIDS-related KS was 35 years (range 20-63 years) and 70 years (range 33-91 years) for those with CKS. Most individuals had an Eastern Cooperative Oncology Group performance status of ≥ 2 (AIDS-related KS 75%; CKS 85%). Seventy-six percent and 40% of individuals with AIDS-related KS and CKS, respectively, received systemic chemotherapy. The most common first-line drug was paclitaxel, with relatively optimal overall response rates (ORRs) for AIDS-related KS (n = 64/72, 89%; ORR 61%) and CKS (n = 24/32, 75%; ORR 50%). The 5-year OS rates were 71% in the AIDS-related KS cohort and 81% in the CKS cohort. The findings from this real-world study may inform clinical practices and highlight the need for increased access to effective treatments and clinical trials for patients with KS in Peru and other developing countries.
Assuntos
Síndrome da Imunodeficiência Adquirida , Sarcoma de Kaposi , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Sarcoma de Kaposi/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Human herpesviruses are enveloped viruses with double-stranded linear DNA genomes highly prevalent in the human population. These viruses are subdivided into three subfamilies, namely alphaherpesvirinae (herpes simplex virus type 1, HSV-1; herpes simplex virus type 2, HSV-2; and varicella-zoster virus, VZV), betaherpesvirinae (human cytomegalovirus, HCMV; human herpesvirus 6, HHV-6; and human herpesvirus 7, HHV-7) and gammaherpesvirinae (Epstein-Barr virus, EBV; and Kaposi's sarcoma-associated herpesvirus, KSHV). Besides encoding numerous molecular determinants to evade the host antiviral responses, these viruses also modulate cellular metabolic processes to promote their replication. Here, we review and discuss existing studies describing an interplay between carbohydrate metabolism and the replication cycle of herpesviruses, altogether highlighting potentially new molecular targets based on these interactions that could be used to block herpesvirus infections.
RESUMO
When tumoral cell expansion exceeds the vascular supply, regions of hypoxia or low oxygen concentration are generated promoting the formation of new vessels through cell proliferation and migration. Viral G protein-coupled receptor (vGPCR) is associated to Kaposi's sarcoma pathology and induces a paracrine transformation when is stably expressed in murine endothelial cells activating hypoxia-induced transcription factors. Previously, we reported the antiproliferative actions of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in endothelial cells transformed by the vGPCR (SVEC-vGPCR). Herein, we further investigated if pro-angiogenic factors as AP-1, HIF-1α and VEGF are modulated by 1α,25(OH)2D3. We found by qRT-PCR analysis that the mRNA level of JunB, a negative regulator of cell proliferation, was similarly increased at all-time points tested after 1α,25(OH)2D3 treatment in SVEC-vGPCR cells. Also, mRNA levels of the pro-angiogenic factor c-Fos, which induces tumor invasion, were only decreased during one short period treatment. In addition, Hif-1α mRNA and protein levels were significantly reduced after 1α,25(OH)2D3 treatment in a VDR dependent fashion. However, mRNA levels of the angiogenic activator Vegf, promoted in turn by Hif-1α expression, were surprisingly high depending on VDR expression as well. Moreover, Egr-1, which has been reported to induce VEGF expression independently of HIF-1α, diminished its expression with 1α,25(OH)2D3 treatment, fact that was related to the decline of p-ERK1/2. Altogether, these results suggest a negative modulation of some pro-angiogenic factors like AP-1 and HIF-1α, as part of the antiproliferative mechanism of 1α,25(OH)2D3 in SVEC-vGPCR endothelial cells.