RESUMEN
Little is known about long-term maintenance of virologic suppression in HIV migrants in Italy. The study aims to compare virologic failure rates and associated factors among antiretroviral therapy (ART)-naïve migrants and natives enrolled in the ARCA database since 2007 who achieved virologic suppression within 18 months from the beginning of the ART. Kaplan-Meier method assessed the probability of virologic suppression and failure. Cox regression model was used for multivariate analysis. Of 2515 patients, 2020 (80.3%) were Italian, 286 (10.6%) migrants from low-income countries, of whom 201 (75.0%) from Africa, and 227 (9.0%) from high-income-countries. The median follow-up was 4.5 years (IQR 2.5-7). No difference was observed in the time of achievement of virological suppression in the three groups (log-rank: p = 0.5687). Higher probability of virologic failure was observed in Africans compared to Italians, to patients from high-income-countries and from low-income-countries other than Africans (Log-rank = p < 0.001). In the adjusted analysis, a higher virologic failure risk was found in Africans only compared to Italians. [HR 4.01; 95% CI 2.44-6.56, p < 0.001]. In Italy, African migrants are less likely to maintain virologic suppression compared to natives and other migrants. Targeted interventions could be needed for foreigners, especially for Africans.
Asunto(s)
Infecciones por VIH , VIH-1 , Migrantes , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Humanos , Italia , Carga ViralRESUMEN
BACKGROUND: Amebiasis is a rare condition in developed countries but epidemiologically growing. Clinical manifestation may range from asymptomatic to invasive disease, amoebic liver abscess being the most common manifestation. We report a peculiar case of left hepatic amoebic liver abscess in a patient without a well-known source of infection and presenting with left portal vein thrombosis. CASE PRESENTATION: Patient, working as longshoreman, presented with complaints of remittent-intermittent fever lasting from 2 weeks. Physical examination was normal. Blood tests showed mild anemia, neutrophilic leukocytosis and elevated inflammation markers. Chest x-rays was normal. Abdominal ultrasound showed multiple hypoechoic liver masses. CT-scan of abdomen showed enlarged left liver lobe due to the presence of large abscess cavity along with thrombosis of left portal vein. The indirect hemagglutination test for the detection of antibodies to Entamoeba histolytica (Eh) was positive. Ultrasound-guided percutaneous drainage revealed "anchovy sauce" pus. Metronidazole and a follow up imaging at 3 months showed resolution of abscess cavity. CONCLUSION: This case shows that amoebic liver abscess is possible even in first world country patients without travel history. Left sided abscess and portal vein thrombosis are rare and hence reported.
Asunto(s)
Entamoeba histolytica , Absceso Hepático Amebiano , Humanos , Italia , Absceso Hepático Amebiano/diagnóstico por imagen , Absceso Hepático Amebiano/tratamiento farmacológico , Metronidazol , UltrasonografíaRESUMEN
Retention in care is a key feature of the cascade of continuum of care, playing an important role in achieving therapeutic success and being crucial for reduction of HIV transmission. The aim of this study was to evaluate the rate of retention in care in a large referral centre in the North of Italy and to identify predictors associated with failed retention. All new HIV-infected subjects were consecutive enrolled from 1 January 2008 to 31 December 2014. Demographics, immune-virological status, hepatitis co-infection and timing of initiation of combined antiretroviral therapy (cART) data were collected at baseline and at the time of last observation. Failed retention in care was defined as lack of laboratory data, clinical visits and drug dispensation for more than 6 months from the last visit. Cox regression analysis was used. Multivariate analysis of variables with P<0.05 in univariate analysis was performed. We enrolled 269 patients (mean age 46.1 years). Males were 197 (73%), Italian 219 (81%) with mean length of disease of 5.1 years. cART was prescribed for 257 patients (95%). The rate of retention in care was 78.4% and the rate of virological suppression was 75%. Predictors of being loss to follow-up were foreign origin (P = 0.048), CD4+ count <200/mmc (P = 0.001) and not being treated for HIV infection (P = 0.0004). Predictors of cART efficacy were shorter duration of HIV infection and baseline HIV-RNA <100 000 copies/ml. These findings underline the necessity to improve retention in care by identifying groups at increased risk of being loss to follow-up. Retention in care of vulnerable population is crucial to reach 90-90-90 UNAIDS endpoint.
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Antirretrovirales/uso terapéutico , Coinfección/epidemiología , Infecciones por VIH/tratamiento farmacológico , Hepatitis/epidemiología , Retención en el Cuidado/estadística & datos numéricos , Adulto , Femenino , Hospitales Comunitarios , Hospitales Universitarios , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Control of HIV replication in elite controller (EC) and long-term nonprogressor (LTNP) patients has been associated with efficient CD8(+)cytotoxic T-lymphocyte function. However, innate immunity may play a role in HIV control. We studied the expression of natural cytotoxicity receptors (NKp46, NKp30, and NKp44) and their induction over a short time frame (2-4 d) on activation of natural killer (NK) cells in 31 HIV controller patients (15 ECs, 16 LTNPs). In EC/LTNP, induction of NKp46 expression was normal but short (2 d), and NKp30 was induced to lower levels vs. healthy donors. Notably, in antiretroviral-treated aviremic progressor patients (TAPPs), no induction of NKp46 or NKp30 expression occurred. More importantly, EC/LTNP failed to induce expression of NKp44, a receptor efficiently induced in activated NK cells in TAPPs. The specific lack of NKp44 expression resulted in sharply decreased capability of killing target cells by NKp44, whereas TAPPs had conserved NKp44-mediated lysis. Importantly, conserved NK cell responses, accompanied by a selective defect in the NKp44-activating pathway, may result in lack of killing of uninfected CD4(+)NKp44Ligand(+) cells when induced by HIVgp41 peptide-S3, representing a relevant mechanism of CD4(+) depletion. In addition, peripheral NK cells from EC/LTNP had increased NKG2D expression, significant HLA-DR up-regulation, and a mature (NKG2A-CD57(+)killer cell Ig-like receptor(+)CD85j(+)) phenotype, with cytolytic function also against immature dendritic cells. Thus, NK cells in EC/LTNP can maintain substantially unchanged functional capabilities, whereas the lack of NKp44 induction may be related to CD4 maintenance, representing a hallmark of these patients.
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Infecciones por VIH/inmunología , Sobrevivientes de VIH a Largo Plazo , Inmunidad Innata/inmunología , Interleucina-2/inmunología , Células Asesinas Naturales/inmunología , Receptor 2 Gatillante de la Citotoxidad Natural/metabolismo , Anticuerpos Monoclonales/inmunología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Inmunofenotipificación , Interleucina-2/metabolismo , Células Asesinas Naturales/citología , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Estadísticas no ParamétricasRESUMEN
BACKGROUND: It has been recently shown that during therapeutic apheresis procedure, a large amount of soluble HLA class I molecules settles onto plastic apheresis circuits, inducing sustained TGFß1 pre/post-transcriptional modulation in activated patients' leukocytes. Reportedly, donors' leukocytes may be exposed to similar immunosuppressing activities during donor apheresis procedures. On this basis, it could be hypothesized that such events can cause immune modulation. It is uncertain which blood cell population is most impacted by these events. This study is focused on the effects on the T lymphocytes. STUDY DESIGN AND METHODS: To assess if such events occur, lymphocytes from 20 apheresis donors collected before and after three closely timed plasma and platelet donation procedures were analyzed for sHLA-I mediated immunomodulation. RESULTS: The results confirmed that sHLA-I molecules bind to the apheresis circuit surfaces. Circuits can also transiently activate donors' CD8(+) T lymphocytes, to which sHLA-I molecules can bind, thus modulating short-lasting immune effects, such as transcriptional and post-transcriptional TGFß1 modulation and soluble Fas ligand release. However, no significant change in relative proportions, absolute number and cell viability of lymphocyte subpopulations was found and no ex vivo immune effect was detectable longer than 14 days after procedure in any cell type in all donors. CONCLUSION: Short-lived sHLA-I mediated immunomodulation was demonstrable in lymphocytes from every donor as a consequence of apheresis procedures, but no enrolled subject experienced any adverse reaction or showed any sign of immunosuppression during 24 months of follow-up after the donations.
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Donantes de Sangre , Plaquetas/citología , Inmunomodulación , Plaquetoferesis/métodos , Anticuerpos Monoclonales/química , Proteína Ligando Fas/sangre , Femenino , Citometría de Flujo , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Leucocitos/metabolismo , Activación de Linfocitos , Masculino , Microscopía Fluorescente , Plasma/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/sangreRESUMEN
We describe the genotypes and allele distribution of interleukin 28B (IL28B) rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in hepatitis C virus (HCV) G1-4 infected patients, to assess predictive ability and to determine whether the combined determination of two IL28B SNPs might improve sustained virologic response (SVR) prediction of both in HCV mono- and HIV/HCV co-infected patients. IL28B SNPs were genotyped in 269 patients, 181 mono- and 88 co-infected, treated with pegylated interferon and ribavirin. Data stratified by HCV mono- and HCV/HIV co-infected patients showed that 58% and 31% of the rs12979860CC carriers and 49% and 21% of the rs8099917TT carriers had SVR. IL28B SNPs, HCV mono-infection and HCV RNA load were associated with SVR as independent predictors in the two study groups as a whole. ROC curve analyses in the two populations separately, based on gender, age, baseline HCV RNA load and rs12979860/rs8099917 revealed similar receiver operating characteristics (ROC) areas under the curve values. Combining the determination of IL28B SNPs, rs8099917 genotyping improved the response prediction in rs12979860CT carriers only in mono-infected patients. In the era of direct-acting antiviral agents, adopting SVR baseline predictors to orientate naïve-patient management represents an important issue. A model involving IL28B SNPs appears able to predict SVR in both populations.
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Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Adulto , Coinfección/tratamiento farmacológico , Coinfección/genética , Coinfección/virología , Quimioterapia Combinada , Femenino , Genotipo , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/genética , VIH-1/aislamiento & purificación , VIH-1/fisiología , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepacivirus/fisiología , Hepatitis C/genética , Hepatitis C/virología , Humanos , Interferón-alfa/uso terapéutico , Interferones , Masculino , Persona de Mediana Edad , Ribavirina/uso terapéutico , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod. OBJECTIVE: The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints. EXPERIMENTAL DESIGN: GX301 was administered by intradermally injecting 500 µg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization. RESULTS: No grade 3-4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses. CONCLUSION: GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.
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Vacunas contra el Cáncer/administración & dosificación , Neoplasias Renales/inmunología , Neoplasias Renales/terapia , Péptidos/administración & dosificación , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/terapia , Adyuvantes Inmunológicos , Anciano , Anciano de 80 o más Años , Aminoquinolinas/inmunología , Antígenos de Neoplasias/química , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/inmunología , Proliferación Celular , Terapia Combinada , Citotoxicidad Inmunológica , Humanos , Imiquimod , Interferón gamma/metabolismo , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Manitol/análogos & derivados , Manitol/inmunología , Persona de Mediana Edad , Estadificación de Neoplasias , Ácidos Oléicos/inmunología , Péptidos/efectos adversos , Péptidos/inmunología , Fenotipo , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Telomerasa/química , Telomerasa/inmunología , Resultado del TratamientoRESUMEN
In early HIV-1 infection, Vdelta1 T lymphocytes are increased in peripheral blood and this is related to chemokine receptor expression, chemokine response, and recirculation. Herein we show that, at variance with healthy donors, in HIV-1-infected patients ex vivo-isolated Vdelta1 T cells display cytoplasmic interferon-gamma (IFN-gamma). Interestingly, these cells coexpress cytoplasmic interleukin-17 (IL-17), and bear the CD27 surface marker of the memory T-cell subset. Vdelta1 T cells, isolated from either patients or healthy donors, can proliferate and produce IFN-gamma and IL-17 in response to Candida albicans in vitro, whereas Vdelta2 T cells respond with proliferation and IFN-gamma/IL-17 production to mycobacterial or phosphate antigens. These IFN-gamma/IL-17 double-producer gammadelta T cells express the Th17 RORC and the Th1 TXB21 transcription factors and bear the CCR7 homing receptor and the CD161 molecule that are involved in gammadelta T-cell transendothelial migration. Moreover, Vdelta1 T cells responding to C albicans express the chemokine receptors CCR4 and CCR6. This specifically equipped circulating memory gammadelta T-cell population might play an important role in the control of HIV-1 spreading and in the defense against opportunistic infections, possibly contributing to compensate for the impairment of CD4(+) T cells.
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Candida albicans/inmunología , Infecciones por VIH/inmunología , VIH-1 , Interferón gamma/biosíntesis , Interleucina-17/biosíntesis , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Femenino , Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T , Humanos , Interleucina-17/genética , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Subfamilia B de Receptores Similares a Lectina de Células NK/análisis , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Receptores CCR4/análisis , Receptores CCR6/análisis , Receptores CCR7/análisis , Receptores de Ácido Retinoico/análisis , Receptores de Hormona Tiroidea/análisis , Subgrupos de Linfocitos T/metabolismo , Factores de Transcripción/análisis , Adulto JovenRESUMEN
BACKGROUND: Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders; among others, they could decrease pro-inflammatory cytokine levels and also induce anti-inflammatory cytokines. MATERIALS AND METHODS: Ex vivo analysis of cells from ten IVIG recipients showed significant increase of IL-10 mRNA and intra-cellular IL-10 molecules in both leukotypes. RESULTS: In vitro comparable results were obtained incubating CD8(+) T lymphocytes and neutrophils from healthy donors with IVIG. sHLA-I and/or sFasL immunodepletion abolished IL-10 modulation. Co-culture with contaminant-free IgM or MabThera did not exert any mRNA modulation. Finally, IgM or MabThera plus purified sHLA-I molecules enhanced IL-10-mRNA in both leukotypes to levels comparable to those obtained with IVIG incubation. CONCLUSION: As IVIG infusion involves administration of soluble contaminants, these data consent to speculate that IVIG might modulate IL-10 via the immunomodulatory activities of sHLA-I contaminant molecules inducing transcriptional and post-transcriptional modulation of IL-10 in CD8(+) T lymphocytes and neutrophils.
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Síndrome de Fatiga Crónica/terapia , Infecciones por VIH/terapia , VIH/inmunología , Antígenos de Histocompatibilidad Clase I/farmacología , Inmunoglobulinas Intravenosas/farmacología , Inmunoterapia , Interleucina-10/biosíntesis , Vasculitis Sistémica/terapia , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Separación Celular , Células Cultivadas , Contaminación de Medicamentos , Proteína Ligando Fas/metabolismo , Proteína Ligando Fas/farmacología , Síndrome de Fatiga Crónica/inmunología , Citometría de Flujo , VIH/patogenicidad , Infecciones por VIH/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Inmunoglobulinas Intravenosas/metabolismo , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Neutrófilos/patología , Vasculitis Sistémica/inmunología , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
We have reported that serum level of soluble HLA-A, -B, -C (sHLA-A,-B,-C) antigens is elevated in HIV-infected subjects and decreases after antiretroviral therapy (HAART). In this study, we measured the levels of soluble HLA-G (sHLA-G) antigens in a cohort of HIV-infected patients before and during HAART. sHLA-G and sHLA-A, -B, -C levels were significantly elevated in HIV-infected subjects as compared with controls before antiretroviral treatment and significantly decreased after 36 months of HAART. sHLA-G levels were correlated with sHLA-A, -B, -C levels, the decrease of plasma HIV-RNA level, the increase of CD4+ T-lymphocyte number and the decrease of CD8+ T-lymphocyte number. These results suggest that the measurement of sHLA-G and sHLA-A, -B, -C antigen serum levels might represent a useful surrogate marker to monitor virological response and immune reconstitution in HIV-positive subjects undergoing HAART treatment.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH/sangre , VIH-1/genética , Antígenos HLA/sangre , Antígenos HLA-A/sangre , Antígenos HLA-B/sangre , Antígenos HLA-C/sangre , Antígenos de Histocompatibilidad Clase I/sangre , Adulto , Biomarcadores/sangre , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/citología , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Antígenos HLA-G , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , ARN Viral/genética , Caracteres Sexuales , Subgrupos de Linfocitos T/citologíaRESUMEN
Integrating evidence from systematic research in daily clinical practice is one of the pillars of evidence-based medicine. Electronic data capture tools simplify data collection from different centers and supports the management of multicenter clinical trials. The Ligurian HIV Network (LHN) is one such tool, originating from a regional effort to integrate clinical trial capabilities for HIV and other chronic infectious diseases. In order to manually collect a complete report of all clinical tests on patients enrolled in a trial, a strenuous human effort and the allocation of great resources would be necessary. Moreover, the risk of error in a manual system is very high. The proposed system automatically extracts clinical data from the EHR of three hospitals of the LHN in a standardized way, and enhance their re-use in clinical trials. Through dedicated questionnaires, physicians reported a strongly positive feedback about the efficacy of the platform in supporting clinical research.
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Registros Electrónicos de Salud , VIH , Informática Médica , Medicina Basada en la Evidencia , Humanos , InvestigaciónRESUMEN
OBJECTIVES: After the skin, the gastrointestinal tract is the second most common target of systemic sclerosis (SSc). AIM: Our aims were to investigate orocecal transit time (OCTT) and the presence of small intestinal bacterial overgrowth (SIBO) in SSc as a cause of intestinal symptoms. METHODS: Fifty-five SSc patients and 60 healthy controls, sex and age matched, entered the study. Enrolled subjects completed a questionnaire for intestinal symptoms and a global symptomatic score (GSS) was calculated. OCTT and the presence of SIBO were assessed by a lactulose breath test (LBT). Patients with SIBO were treated with rifaximin 1,200 mg/day for 10 days. Finally, a second questionnaire and LBT were performed 1 month after the end of therapy. RESULTS: The prevalence of SIBO was higher in SSc patients compared with controls (30/54 vs 4/60, respectively, P < 0.001). OCTT was significantly slower in SSc patients compared with controls (150 min, 25-75th percentile 142.5-165 vs 105 min, 25-75th percentile 90-135, respectively, P < 0.001). In patients with SIBO, the median GSS score was 8 (25-75th percentile 3.25-10.75). Eradication of SIBO was achieved in 73.3% of patients, with a significant reduction of symptoms in 72.7% of them (GSS score 2, 25-75th percentile 1-3, P < 0.05). CONCLUSIONS: These data suggest that SIBO occurs more frequently in SSc patients than in controls. Intestinal symptoms in these patients may be related to this syndrome and its eradication seems useful to improve clinical features. OCTT is significantly delayed in SSc patients, suggesting an impairment of intestinal motility, a further risk factor for the development of SIBO.
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Síndrome del Asa Ciega/tratamiento farmacológico , Esclerodermia Sistémica/complicaciones , Adulto , Anciano , Antiinfecciosos/uso terapéutico , Síndrome del Asa Ciega/epidemiología , Síndrome del Asa Ciega/etiología , Pruebas Respiratorias , Estudios Transversales , Femenino , Tránsito Gastrointestinal , Humanos , Intestino Delgado , Lactulosa , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Rifamicinas/uso terapéutico , Rifaximina , Esclerodermia Sistémica/epidemiología , Resultado del TratamientoRESUMEN
Human major histocompatibility complex class I antigens (HLA-A, -B, and -C) are heterodimeric molecules composed of a alpha heavy chain noncovalently associated with an invariant protein known as beta(2)-microglobulin. Beside being expressed on the membrane of the large majority of nucleated cells, HLA class I antigens are evident in serum (sHLA-I). We have previously detected a significant increase in the serum level of beta(2)-microglobulin-associated HLA-I antigens in human immunodeficiency virus (HIV)-infected patients compared with HIV-negative controls. The introduction of highly active antiretroviral therapy (HAART) modified the clinical course of the disease and decreased the acquired immunodeficiency syndrome-related morbidity and mortality. Therefore, we measured the levels of sHLA-I antigens in 64 HIV-infected patients before and during HAART treatment and correlated them with the immunological and virological response to antiretroviral treatment. Serum sHLA-I antigen level was elevated in all HIV-infected patients before and significantly decreased after 36 months of HAART treatment, correlating with the decrease of plasma HIV-RNA level and with the increase of CD4+ T-lymphocyte number. These results suggest that the measurement of sHLA-I antigens serum level might represent a useful surrogate marker to monitor HIV-positive patients undergoing HAART treatment.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Antígenos de Histocompatibilidad Clase I/sangre , Adulto , Recuento de Linfocito CD4 , Femenino , VIH/aislamiento & purificación , Infecciones por VIH/virología , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Resultado del Tratamiento , Carga Viral , Microglobulina beta-2/sangreRESUMEN
HIV treatment is based on combined antiretroviral therapy (cART) which has substantially improved survival, thus resulting in an increase in patient life expectancy as well as in the cost of HIV-related medical care. Therefore, several cost effectiveness studies were implemented worldwide, with one specifically in the Liguria region (Italy), to compare the annual economic expense in this area for HIV services, and the related improvement in patients' health. The IANUA project is intended to implement both cost-effectiveness and cost-utility analysis, therefore data related to clinical indicators and perceived health status were collected, the latter using a questionnaire based on the EQ-5D-3L. Information about the antiretroviral drugs and the relative quantity that a patient withdraws from the hospital pharmacy every month were extracted from the regional "F-file". All data gathered were stored in the Ligurian HIV Network, a web platform developed by the DIBRIS - Medinfo laboratory. More than eight hundred questionnaires were collected, and data will be elaborated by economists and psychologists. The first statistical elaborations showed that, as expected, costs increased as the number of therapeutic lines increased. Moreover, the average annual costs for patients whose last CD4 values were below 200 cells/mmc corresponded to the maximum expense recorded, however, the cost for patients with final CD4 counts above 500 cells/mmc was not, as expected, the lowest found. This can be explained by the fact that stabilized patients, who had CD4 values below 500 cells/mmc, did not need very expensive care, while patients with CD4 counts above 500 cells/mmc improved their health status thanks to cART.
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Terapia Antirretroviral Altamente Activa/economía , Infecciones por VIH/economía , Infecciones por VIH/prevención & control , Costos de la Atención en Salud/estadística & datos numéricos , Programas Médicos Regionales/economía , Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Análisis Costo-Beneficio , Infecciones por VIH/epidemiología , Humanos , Italia/epidemiología , Evaluación de Programas y Proyectos de Salud , Programas Médicos Regionales/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Nonantigen specific CD8+ suppressor T lymphocytes (CD8+ Ts) inhibit T-cell proliferation of antigen-specific T lymphocytes. The impossibility to generate in vitro these cells has been correlated with the appearance of relapses in patients affected by autoimmune diseases, suggesting the involvement of these cells in immune regulation. This study was aimed to identify circulating precursors and to characterize the phenotype and mechanism of action of CD8+ Ts. We found that CD8+ Ts can be generated in vitro from CD8+CD28- T lymphocytes, but not from CD8+CD28+ T cells. A key role in their generation is played by monocytes that secrete interleukin-10 (IL-10) after granulocyte macrophage-colony-stimulating factor (GM-CSF) stimulation. Cell-to-cell direct interaction between CD8+CD28- T cells and monocytes does not play a role in the generation of CD8+ Ts. CD8+ Ts have a CD45RA+, CD27-, CCR7-, IL-10Ralpha+ phenotype and a TCR Vbeta chain repertoire overlapping that of autologous circulating CD8+ T cells. This phenotype is typical of T lymphocytes previously expanded due to antigen stimulation. Their suppressive effect on T-cell proliferation targets both antigen presenting cells, such as dendritic cells, and antigen-specific T lymphocytes, and is mediated by IL-10. CD8+ Ts suppress also the antigen-specific cytotoxic activity of CTL decreasing the expression of HLA class I molecules on target cells through IL-10 secretion. These findings can be helpful for the better understanding of immune regulatory circuits and for the definition of new pathogenic aspects in autoimmunity and tumor immunology.
Asunto(s)
Antígenos CD28/inmunología , Linfocitos T CD8-positivos/inmunología , Tolerancia Inmunológica/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T/inmunología , Anticuerpos Monoclonales/farmacología , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Presentación de Antígeno/efectos de los fármacos , Presentación de Antígeno/inmunología , Antígenos CD28/análisis , Complejo CD3/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Antígenos CD8/análisis , Linfocitos T CD8-positivos/efectos de los fármacos , Comunicación Celular/inmunología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Tolerancia Inmunológica/fisiología , Interleucina-10/inmunología , Interleucina-10/metabolismo , Interleucina-10/fisiología , Interleucina-2/farmacología , Antígenos Comunes de Leucocito/análisis , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Activación de Linfocitos/fisiología , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/efectos de la radiación , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Receptores CCR7 , Receptores de Quimiocina/análisis , Receptores de Interleucina/análisis , Receptores de Interleucina-10 , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/efectos de los fármacos , Tuberculina/inmunologíaRESUMEN
Resident macrophages are mainly responsible for the clearance of apoptotic cells from tissue by phagocytosis. Phagocytosis of apoptotic cells is not accompanied by activation of inflammatory mechanisms, unlike what happens when necrotic phenomena occur. We analyzed the effect of phagocytosis of apoptotic bodies on macrophage cell functions. After phagocytosis of apoptotic cells macrophages were unable to present an exogenous antigen to autologous antigen-specific T-cell lines. The inhibition was mediated by different mechanisms including binding of apoptotic DNA to human leukocyte antigen (HLA) class II molecules of macrophages, decreased expression of co-stimulatory molecules and increased secretion of tumor growth factor beta (TGFbeta). When dendritic cells were cultured with macrophages phagocytosing apoptotic cells, or with their supernatant, impaired dendritic cell antigen presenting activity and reduced tumor necrosis factor alpha (TNFalpha) secretion were found. Our results suggest that: (1) the phagocytosis of apoptotic bodies inhibits macrophage antigen presentation; (2) such inhibition is mediated by the binding of apoptotic DNA to macrophage HLA class II molecules as well as by the activation of biological mechanisms that induce an anti-inflammatory functional behavior in macrophages; and (3) macrophages phagocytosing apoptotic cells inhibit antigen presentation of neighboring dendritic cells via TGFbeta secretion. These events are likely related to the preservation of healthy tissues from the onset of inflammation.
Asunto(s)
Presentación de Antígeno/inmunología , Apoptosis/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Macrófagos/inmunología , Fagocitosis/inmunología , Humanos , Células Jurkat , Macrófagos/citología , Macrófagos/metabolismo , Fagocitos/inmunologíaRESUMEN
Cases of acute hepatitis induced by statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been reported. A 65-year-old woman was admitted to our hospital because of fatigue, jaundice and altered liver function tests while on treatment with atorvastatin. On the basis of clinical, serological and histological findings, a score leading to a diagnosis of autoimmune hepatitis was reached. We suggest that atorvastatin may have revealed an underlying autoimmune hepatitis.
Asunto(s)
Enfermedades Autoinmunes/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Ácidos Heptanoicos/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Pirroles/efectos adversos , Anciano , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , Atorvastatina , Enfermedades Autoinmunes/patología , Bilirrubina/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Femenino , Humanos , Hígado/patología , Pruebas de Función HepáticaAsunto(s)
Seudoobstrucción Intestinal/etiología , Fallo Hepático/etiología , Protoporfiria Eritropoyética/complicaciones , Resinas de Intercambio Aniónico/uso terapéutico , Carbón Orgánico/uso terapéutico , Colagogos y Coleréticos/uso terapéutico , Resina de Colestiramina/uso terapéutico , Hemina/uso terapéutico , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Intercambio Plasmático , Protoporfiria Eritropoyética/diagnóstico , Protoporfiria Eritropoyética/terapia , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
BACKGROUND: The cause of transfusion-related immunomodulation (TRIM) has proved tantalisingly elusive. An ever-growing body of evidence indicates that the infusion of large amounts of soluble and cell-associated antigens into a recipient can somehow induce TRIM. One soluble molecule that has been implicated in TRIM is soluble human leucocyte antigen I (sHLA-I). However, patients infused with large amounts of sHLA-I do not always and unambiguously experience TRIM. As soluble CD8 (sCD8) molecules have been shown to capable of binding membrane and soluble HLA-I molecules, we focused on sCD8 as a possible modulator of sHLA-I-mediated TRIM. MATERIAL AND METHODS: To this aim we compared the up-regulation of circulating sCD8 in plasma from patients suffering from the same pathology, but chronically transfused with two different blood derivatives: pre- and post-storage leucodepleted red blood cells which contain low and high levels of contaminating sHLA-I, respectively. RESULTS: Significantly larger amounts of sCD8 circulating molecules were detectable in the plasma of patients transfused with post-storage leucodepleted red blood cells whose supernatants contained significantly larger amounts of sHLA-I contaminating molecules. CONCLUSION: With the limitation of indirect evidence, this report introduces a new facet of the bioactivity of sCD8 as a possible modulator of sHLA-I-mediated TRIM.