Search

Background Kaposi Sarcoma (KS) has been historically associated with HIV, especially in people with advanced immunosuppression. Its prevalence decreased over time, but management remains difficult especially when the diagnosis is late and there is a visceral involvement. Bone localization, and particularly the vertebral one, is rare. We herein present a case of vertebral localizations of KS and performed a review literature to assess demographic, clinical characteristics and treatment outcomes in people with HIV. Methods The systematic review was carried out by following the PRISMA guidelines and registering the protocol in PROSPERO database (n. registration: CRD42024548626). We included all cases of vertebral localizations of KS from January 1rst 1981 to December 31rst, 2023. Results Twenty-two cases, including ours, were ever reported in people with HIV, mostly males (95.4%), with a median age of 35 years (IQR: 32-44), median CD4+ T cell count of 80 cell/mm3 (IQR 13-111), 31.8% with high HIV viral load. Five people received HIV and KS diagnosis simultaneously. In all cases, but one, there were multiple sites involved. Most spine lesions were localized at thoracic and lumbar levels (59.1%), causing pathological fractures in 2 cases. Chemotherapy and radiotherapy were performed in 50% and 18.2% cases, respectively. 22.7% persons died, stability and improvement/disease regression were reported for 13.6% and 22.7% persons, respectively, while 9.9% had a significant disease progression and a person was lost to follow-up. Conclusions Despite progresses in treatment, late presentation of KS, especially with spine involvement may have a poor prognosis. More efforts are needed to promote access to HIV testing, especially when indicating conditions are present.

The spectrum of lymphoproliferative disorders linked to human herpesvirus 8 (HHV-8) infection has been constantly increasing since the discovery of its first etiologic association with primary effusion lymphoma (PEL). PEL is a rapidly progressing non-Hodgkin’s B-cell lymphoma that develops in body cavities in an effusional form. With the increase in the overall survival of PEL patients, as well as the introduction of HHV-8 surveillance in immunocompromised patients, the extracavitary, solid counterpart of PEL was later identified. Moreover, virtually all plasmablastic variants of multicentric Castleman’s disease (MCD) developing in HIV-1-infected individuals harbor HHV-8, providing a strong etiologic link between MCD and this oncogenic herpesvirus. Two other pathological conditions develop in HIV-1-infected persons concomitantly with MCD: MCD with plasmablastic clusters and MCD-associated plasmablastic lymphoma, the first likely representing an intermediate stage preceding the full neoplastic stage. MCD in leukemic phase has also been described, albeit much less commonly. The germinotropic lymphoproliferative disorder (GLPD) may resemble extracavitary PEL, but develops in immune competent HHV8-infected individuals, and, unlike the disorders described above, it responds well to conventional therapies. Almost all HHV-8-mediated lymphoproliferative disorders are the result of an interaction between HHV-8 infection and a dysregulated immunological system, leading to the formation of inflammatory niches in which B cells, at different developmental stages, are infected, proliferate and may eventually shift from a polyclonal state to a monoclonal/neoplastic disorder. Herein, we describe the association between HHV-8 and lymphoproliferative disorders and highlight the predominant distinctive features of each disease.

Adult T cell Leukemia/Lymphoma (ATLL) is a mature T cell malignancy associated with Human T cell Leukemia Virus type 1 (HTLV-1) infection. Among its four main clinical subtypes, the prognosis of acute and lymphoma variants remains poor. The long latency (3–6 decades) and low incidence (3–5%) of ATLL imply the involvement of viral and host factors in full-blown malignancy. Despite multiple preclinical and clinical studies, the contribution of the stromal microenvironment in ATLL development is not yet completely unraveled. The aims of this study were to investigate the role of the host microenvironment, and specifically fibroblasts, in ATLL pathogenesis and to propose a murine model for the lymphoma subtype. Here we present evidence that the oncogenic capacity of HTLV-1-immortalized C91/PL cells is enhanced when they are xenotransplanted together with human foreskin fibroblasts (HFF) in immunocompromised BALB/c Rag2-/-γc-/- mice. Moreover, cell lines derived from a developed lymphoma and their subsequent in vivo passages acquired the stable property to induce aggressive T cell lymphomas. In particular, one of these cell lines, C91/III cells, consistently induced aggressive lymphomas also in NOD/SCID/IL2Rγc KO (NSG) mice. To dissect the mechanisms linked to this enhanced tumorigenic ability, we quantified 45 soluble factors released by these cell lines and found that 21 of them, mainly pro-inflammatory cytokines and chemokines, were significantly increased in C91/III cells compared to the parental C91/PL cells. Moreover, many of the increased factors were also released by human fibroblasts and belonged to the known secretory pattern of ATLL cells. C91/PL cells co-cultured with HFF showed features reminiscent of those observed in C91/III cells, including a similar secretory pattern and a more aggressive behavior in vivo. On the whole, our data provide evidence that fibroblasts, one of the major stromal components, might enhance tumorigenesis of HTLV-1-infected and immortalized T cells, thus throwing light on the role of microenvironment contribution in ATLL pathogenesis. We also propose that the lymphoma induced in NSG mice by injection with C91/III cells represents a new murine preclinical ATLL model that could be adopted to test novel therapeutic interventions for the aggressive lymphoma subtype.

Limonoids are human health promoters, and have many pharmacological properties: anticancer, antioxidant, antibacterial and antifungal. To the best of the authors' knowledge, there are no previous reports on the composition of limonoids in bergamot fruits, so the aim of this work was to characterize bergamot peel, pulp, seed and juice. Samples analysed showed the presence of both limonoids aglycones and glucosides. Limonoid aglycones are the most abundant in seeds and peels (70 and 80% of the total, respectively), while limonoid glucosides are the more abundant in juices and pulps (61 and 76% of the total, respectively). Moreover a method to isolate pure limonoids from bergamot seeds and juice by means of a 2D-HPLC/PDA/MS preparative system is proposed. Pure molecules isolated were used to build calibration curves to quantify limonoids in real samples. Isolation of nutraceuticals from seeds and juices can represent an advantageous way to re-evaluate these by-products.

BackgroundHuman herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS) and of some lymphoproliferative disorders of B cells. Most malignancies develop after long-lasting viral dormancy, and a preventing role for both humoral and cellular immune control is suggested by the high frequency of these pathologies in immunosuppressed patients. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8-infected individuals with and without cKS.Methodology/principal findingsCirculating B cells and their subsets were analyzed by 6-color flow cytometry in the following groups: 1- patients HHV-8 positive with classic KS (cKS) (n = 47); 2- subjects HHV-8 positive and cKS negative (HSP) (n = 10); 3- healthy controls, HHV-8 negative and cKS negative (HC) (n = 43). The number of B cells belonging to the preimmune/natural effector compartment, including transitional, pre-naïve, naïve and MZ-like subsets, was significantly higher among HHV-8 positive subjects, with or without cKS, while was comparable to healthy controls in the antigen-experienced T-cell dependent compartment. The increased number of preimmune/natural effector B cells was associated with increased resistance to spontaneous apoptosis, while it did not correlate with HHV-8 viral load.Conclusions/significanceOur results indicate that long-lasting HHV-8 infection promotes an imbalance in peripheral B cell subsets, perturbing the equilibrium between earlier and later steps of maturation and activation processes. This observation may broaden our understanding of the complex interplay between viral and immune factors leading HHV-8-infected individuals to develop HHV-8-associated malignancies.

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women.