RESUMEN
BACKGROUND AND AIMS: Twin studies have long been used to infer heritability. Within the 'omics era, twin cohorts have even greater research potential. This study describes the formation of the UK IBD Twin Registry and analysis of concordance and environmental factors. METHOD: Twin pairs with IBD were recruited by advertising via IBD charities and social media, re-tracing a dormant IBD database and clinician referral. Details of zygosity, concordance, disease history and environmental factors were assessed. Pair concordance was calculated, and environmental factors were analysed with logistic regression models adjusted for zygosity and concordance. RESULTS: Ninety-one twin pairs were included in the analysis; forty-two with CD and forty-nine with UC. More MZ twin pairs with CD were concordant compared with DZ pairs, thus inferring heritability (Chi-sq. 15.6. P < 0.001). In UC, MZ concordance was also numerically greater. Cigarette smoking was predictive of CD (OR 2.66, 95% CI 1.16 to 6.07 P = 0.02); there may be an independent association with cannabis smoking (OR 2.59 95% CI 0.89 to 7.55 P = 0.08). Breastfeeding was protective against UC (OR 0.48, 95% CI 0.25-0.93, P = 0.03), but not CD. Self-reports of less occurrences of gastroenteritis than peers were protective against future UC onset (OR 0.33 95% CI 0.15 to 0.74, P = 0.01). Method of delivery, parental attitudes towards hygiene and recall of diet did not impact future IBD concordance. CONCLUSIONS: This study supports the heritability of IBD. Twin study analysis was able to elucidate environmental factors associated with IBD.
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Enfermedades Inflamatorias del Intestino , Gemelos Dicigóticos , Enfermedades en Gemelos/epidemiología , Enfermedades en Gemelos/genética , Humanos , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Inflamatorias del Intestino/genética , Sistema de Registros , Factores de Riesgo , Gemelos Monocigóticos/genética , Reino Unido/epidemiologíaRESUMEN
Clostridium difficile is a bacterial infection that colonises the gut in susceptible hosts. It is associated with exposure to healthcare settings and antibiotic use. It could be assumed that cystic fibrosis (CF) patients are a high-risk group for C.difficile. However, despite high carriage rates, CF patients have low rates of active disease. There are guidelines for the treatment of C.difficile, however little is published specific to treating C.difficile in CF. This article provides an overview of the current management strategies for C.difficile in CF, including a description of the first faecal transplantation in this patient population.
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Antibacterianos/efectos adversos , Infecciones por Clostridium , Fibrosis Quística/terapia , Trasplante de Microbiota Fecal/métodos , Antibacterianos/uso terapéutico , Infecciones por Clostridium/etiología , Infecciones por Clostridium/terapia , Humanos , Manejo de Atención al Paciente/métodosRESUMEN
HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++ CD8+ T cells are a tissue-infiltrating population that produce IL17A, IL22, IFN, and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of mucosal associated invariant T (MAIT) cells and have been recently implicated in host defense against pathogens. We analyzed the frequency and function of CD161++ /MAIT cells in peripheral blood and tissue from patients with early stage or chronic-stage HIV infection. We show that the CD161++ /MAIT cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++ /MAIT cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact mucosal defense and could be important in susceptibility to specific opportunistic infections in HIV.
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Infecciones por VIH/inmunología , Inmunidad Mucosa/inmunología , Subfamilia B de Receptores Similares a Lectina de Células NK/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Apoptosis/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/virología , Células Cultivadas , Estudios de Cohortes , Escherichia coli/inmunología , Femenino , Citometría de Flujo , VIH/efectos de los fármacos , VIH/inmunología , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Humanos , Inmunohistoquímica , Interleucina-17/inmunología , Interleucina-17/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/virología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismo , Receptores CCR5/inmunología , Receptores CCR5/metabolismo , Receptores CCR6/inmunología , Receptores CCR6/metabolismo , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/virología , Factores de TiempoRESUMEN
BACKGROUND: Pancreatic carcinoma is often inoperable, carries a poor prognosis, and is commonly complicated by malignant biliary obstruction. Phase I/II studies have demonstrated good safety and early stent patency using endoscopic biliary radiofrequency ablation (RFA) as an adjunct to self-expanding metal stent (SEMS) insertion for biliary decompression. AIM: To analyze the clinical efficacy of endobiliary RFA. METHODS: Retrospective case-control analysis was carried out for 23 patients with surgically unresectable pancreatic carcinoma and malignant biliary obstruction undergoing endoscopic RFA and SEMS insertion and 46 controls (SEMS insertion alone) in a single tertiary care center. Controls were stringently matched for age, sex, metastases, ASA/comorbidities. Survival, morbidity, and stent patency rates were assessed. RESULTS: RFA and control groups were closely matched-ASA 2.35 ± 0.65 versus 2.54 ± 0.50, p = 0.086; metastases 9/23 (39.1%) versus 18/46 (39.1%), p = 0.800; chemotherapy 16/23 (69.6%) versus 24/46 (52.2%), p = 0.203. Median survival in RFA group was 226 days (IQR 140-526 days) versus 123.5 days (IQR 44-328 days) in controls (p = 0.010). RFA was independently predictive of survival at 90 days (OR 21.07, 95% CI 1.45-306.64, p = 0.026) and 180 days (OR 4.48, 95% CI 1.04-19.30, p = 0.044) in multivariate analysis. SEMS patency rates were equivalent in both groups. RFA was well tolerated with minimal side effects. CONCLUSIONS: Endoscopic RFA is a safe and efficacious adjunctive treatment in patients with advanced pancreatic malignancy and biliary obstruction and may confer early survival benefit. Randomized prospective clinical trials of this new modality are mandated.
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Ablación por Catéter , Colangiopancreatografia Retrógrada Endoscópica , Colestasis/cirugía , Neoplasias Pancreáticas/complicaciones , Anciano , Anciano de 80 o más Años , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Distribución de Chi-Cuadrado , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Colangiopancreatografia Retrógrada Endoscópica/mortalidad , Colestasis/diagnóstico , Colestasis/etiología , Colestasis/mortalidad , Drenaje/instrumentación , Femenino , Humanos , Estimación de Kaplan-Meier , Londres , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Stents , Centros de Atención Terciaria , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Intravenous [IV] infliximab is a well-established therapy for inflammatory bowel diseases [IBD] patients. A subcutaneous [SC] formulation of infliximab [CT-P13] has recently been shown to be as effective as IV infliximab after two doses of IV induction in a randomised trial, but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching programme to SC CT-P13 in patients treated with IV infliximab. METHODS: Patients on established maintenance IV infliximab, who switched to SC CT-P13, were included in this retrospective multicentre cohort study. Disease activity was monitored serially with the Harvey-Bradshaw Index [HBI] for Crohn's disease [CD] and the Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis (UC) for up to 12 months at months 3, 6, and 12. Faecal calprotectin [FC] and C-reactive protein [CRP] were recorded at baseline and follow-up, if available. Infliximab trough levels were measured prior to switch and at months 3, 6, and 12 following switch. The primary outcome measure was treatment persistence at latest follow-up. Secondary outcome measures included infliximab pharmacokinetics [PK], safety, need for corticosteroid rescue therapy, and need for surgery. RESULTS: We included 181 patients, of whom 115 [63.5%] had CD. The majority [72.4%] were on 8-weekly dosing of intravenous infliximab prior to switching, and more than half [59.1%] were on concomitant immunomodulatory therapy. The majority of patients (CD: 106, 92.2%; UC: 46, 76.7%; and IBD unclassified [IBD-U]: 5, 83.3%) were in clinical remission. Treatment persistence rate was high [n = 167, 92.3%] and only 14 patients [7.7%] stopped treatment during the follow-up period. There was no significant difference between baseline and repeat measurements at 3, 6, or 12 months for HBI, SCCAI, CRP, or FC. Of the total cohort, 25 patients (13.8%) had perianal CD. Of these, only two patients [8%] had worsening of perianal CD and required antibiotic therapy and further examination under anaesthesia [EUA]. Both these patients also switched back to intravenous infliximab. Median infliximab level increased from a baseline of 8.9 µg/dl [range 0.4-16] to 16.0 µg/dl [range 2.3-16, p <0.001] at 3 months. Serum levels stayed stable at 6 months [median 16 µg/dl, range 0.3-17.2] and 12 months [median 16 µg/dl, range 0.3-19.1, both p <0.001 compared with baseline]. Among the variables examined, only antibodies to infliximab [ATI] was associated with infliximab levels (odds ratio [OR] -13.369, 95% CI -15.405, -11.333, p <0.001]. A total of 14 patients [7.7%] developed ATI; of these, nine [64.3%] were on concomitant immunomodulatory therapy. Immunomodulatory therapy was not significantly associated with development of ATI [p = 0.15]. In a subset of patients receiving escalated IV infliximab dosing frequency prior to switching, no difference in treatment persistence was observed in patients receiving weekly versus alternate weekly SC CT-P13. Patient acceptance and satisfaction rates with SC CT-P13 were very high. CONCLUSIONS: Among patients on IV infliximab maintenance therapy switched to SC CT-P13, we observed high treatment persistence rates and low rates of immunogenicity, with no change in clinical disease activity indices or biomarkers. Infliximab levels increased after switch to SC CT-P13, and only ATI was associated with serum infliximab levels. Patient acceptance and satisfaction rates were high with SC CT-P13.
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Biosimilares Farmacéuticos , Colitis Ulcerosa , Colitis , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Anticuerpos Monoclonales/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Colitis/inducido químicamente , Enfermedad de Crohn/diagnóstico , Sustitución de Medicamentos , Fármacos Gastrointestinales/uso terapéutico , Humanos , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Complejo de Antígeno L1 de Leucocito , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: In unresectable malignant bile duct obstruction in a patient with a life expectancy longer than 3 months, the use of self-expandable metal stents (SEMSs) is the standard technique to ensure continued biliary drainage. As many as 50% of patients with SEMSs will present with stent occlusion within 6 months. Changes to stent design and composition and concomitant therapy have failed to improve stent patency; therefore, alternative techniques to safely prolong stent patency are required. OBJECTIVE: To demonstrate the safety of endobiliary bipolar radiofrequency ablation (RFA) in patients with malignant biliary obstruction and to report the 90-day biliary patency of this novel procedure. DESIGN: Open-label pilot study. SETTING: Single tertiary care unit. PATIENTS: A total of 22 patients with unresectable malignant bile duct obstruction. INTERVENTIONS: Bipolar RFA within the bile duct. MAIN OUTCOME MEASUREMENTS: Immediate and 30-day complications and 90-day stent patency. RESULTS: A total of 22 patients (16 pancreatic, 6 cholangiocarcinoma) were recruited between January 2009 and April 2010. Deployment of an RFA catheter was successful in 21 patients. SEMS placement was achieved in all cases of successful RFA catheter deployment. One patient failed to demonstrate successful biliary decompression after SEMS placement and died within 90 days. All other patients maintained stent patency at 30 days. One patient had asymptomatic biochemical pancreatitis, 2 patients required percutaneous gallbladder drainage, and 1 patient developed rigors. At 90-day follow-up, 1 additional patient had died with a patent stent, and 3 patients had occluded biliary stents. LIMITATIONS: Cohort study. CONCLUSIONS: Endobiliary RFA treatment appears to be safe. Randomized studies with prolonged follow-up are warranted.
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Neoplasias de los Conductos Biliares/cirugía , Ablación por Catéter , Colangiopancreatografia Retrógrada Endoscópica , Colestasis/cirugía , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/complicaciones , Colestasis/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Resultado del TratamientoRESUMEN
We have characterized an assay measuring CD8 T cell-mediated inhibition of human immunodeficiency virus (HIV) type 1 replication, demonstrating specificity and reproducibility and employing a panel of primary HIV-1 isolates. The assay uses relatively simple autologous cell culture and enzyme-linked immunosorbent assay, avoids generation of T cell clones, and can be performed with <2 million peripheral blood mononuclear cells. Efficient CD8 T cell-mediated cross-clade inhibition of HIV-1 replication in vitro was demonstrated in antiretroviral therapy-naive HIV-1-infected subjects with controlled viral replication in vivo but not in viremic subjects. An HIV-1 vaccine candidate, consisting of DNA and recombinant adenovirus 5 vectors tested in a phase I clinical trial, induced CD8 T cells that efficiently inhibited HIV-1 in a HLA-I-dependent manner. Assessment of direct antiviral T cell function by this assay provides additional information to guide vaccine design and the prioritizing of candidates for further clinical trials.
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Vacunas contra el SIDA/inmunología , Linfocitos T CD8-positivos/inmunología , VIH-1/inmunología , Pruebas de Neutralización/métodos , Vacunas contra el SIDA/genética , Adenovirus Humanos/genética , Adulto , Anciano , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Vectores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Replicación Viral/inmunologíaRESUMEN
INTRODUCTION: Antitumour necrosis factor (TNF) agents and vedolizumab are used to treat ulcerative colitis (UC) but the response is variable and there is little data on comparative effectiveness. Apart from previous exposure to anti-TNF agents, predictors of response have not been identified. We aimed to (i) compare the efficacy of anti-TNF agents and vedolizumab in UC and (ii) investigate the utility of clinical and biochemical parameters in predicting response. PATIENTS AND METHODS: Patients commencing any biological therapy for ambulant UC were included. Disease activity was monitored serially with the Simple Clinical Colitis Activity Index for up to 12 months. We compared the efficacy of anti-TNF agents and vedolizumab for induction and maintenance of response and remission on an intention-to-treat basis. We examined the utility of faecal calprotectin (FC) and early normalization of FC to predict response. RESULTS: Ninety-seven patients commencing anti-TNF and 42 commencing vedolizumab therapy were included. Vedolizumab-treated patients had significantly greater previous anti-TNF therapy exposure and a lower baseline FC. Response, remission and steroid-free remission rates were comparable between both groups at 6 weeks, 6 and 12 months. Clinical remission but not steroid-free remission at 12 months was higher in the vedolizumab group. There was a significant reduction in the Simple Clinical Colitis Activity Index and FC at 6 weeks, 6 and 12 months compared with baseline in both groups. Baseline FC and early normalization did not predict response at 6 and 12 months. CONCLUSION: The efficacy of anti-TNF and vedolizumab in UC appear comparable. We could not identify any predictors of response and remission.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Adalimumab/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Investigación sobre la Eficacia Comparativa , Femenino , Glucocorticoides/uso terapéutico , Humanos , Infliximab/uso terapéutico , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: HIV-1 infection is known to have a detrimental impact on peripheral blood natural killer cell phenotype and function. Chronic HIV-1 also causes a substantial depletion of CD4+ T cells in the gastrointestinal tract and the blood. OBJECTIVE: To investigate the impact of chronic HIV-1 infection with on natural killer cell populations in the gastrointestinal tract and the effect of suppression of plasma viraemia with antiretroviral therapy. METHODS: Lymphocyte populations were extracted from the lamina propria of biopsies taken from the sigmoid colon of HIV-1-infected and uninfected individuals. The proportions of natural killer cell subsets were compared in viraemic (n = 15) and aviraemic HIV-1-positive, HAART-treated individuals (n = 27) and HIV-1 negative control individuals (n = 26) using flow cytometry on gated subsets. RESULTS: Natural killer cells are depleted in colonic biopsies from HIV-1-infected individuals with detectable plasma virus in comparison with HIV-1-negative individuals. A significant increase in the proportion of both natural killer and CD4+ T cells in the colonic lamina propria is observed in aviraemic individuals compared to viraemic individuals. CONCLUSIONS: Chronic HIV-1 infection results in depletion of both natural killer cells and CD4+ T cells in colonic tissue and antiretroviral therapy results in a recovery of these subsets in individuals with undetectable plasma viral load.
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Colon Sigmoide , Infecciones por VIH/inmunología , VIH-1 , Mucosa Intestinal/inmunología , Células Asesinas Naturales/inmunología , Membrana Mucosa/inmunología , Adulto , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Estudios de Casos y Controles , Citometría de Flujo , Infecciones por VIH/tratamiento farmacológico , Humanos , Recuento de Linfocitos , Persona de Mediana Edad , Estadísticas no Paramétricas , Carga Viral , Viremia/inmunologíaRESUMEN
Anergy and defective immune responses are characteristic of chronic HIV-1 infection. The programmed death 1 (PD-1)/PD-1 ligand (PD-L1) pathway appears to be involved in downregulating T-cell functionality. We found raised levels of PD-L1 in aviraemic chronically infected HIV-1-positive patients, which may contribute to incomplete immune reconstitution after treatment with HAART.
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Antígenos CD/análisis , Terapia Antirretroviral Altamente Activa/métodos , Proteínas Reguladoras de la Apoptosis/análisis , Infecciones por VIH/inmunología , VIH-1/inmunología , Antígeno B7-H1 , Complejo CD3/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/tratamiento farmacológico , Humanos , Recuento de Linfocitos , Receptor de Muerte Celular Programada 1 , Receptores CCR7 , Receptores de Quimiocina/inmunologíaRESUMEN
OBJECTIVES: To determine if the expression of CD38 on CD8+ T-cells could be used as a marker of viral replication <50 copies/ml in peripheral blood. METHODS: In a cross-sectional study of patients attending a single HIV clinic in London, an ultra-sensitive HIV RNA viral load assay, with a limit of detection of 3 copies/ml, was used to determine HIV-1 replication in plasma in 70 patients who had sustained viral suppression <50 copies/ml by bDNA assays. Immune activation using the expression of CD38 on CD8+ T-cells was also assessed in patients on antiretroviral therapy (ART) with sustained viral suppression, individuals with persistent low-level viraemia <400 copies/ml and subjects failing ART (viral load >400 copies/mi). RESULTS: There was no significant difference in the percentage of CD8+CD38++ T-cells between patients with <50 copies or <3 copies/ml. Immune activation was significantly increased in patients with persistent low-level viraemia and in subjects failing ART. CD4+ T-cell counts in patients on long-term successful ART are inversely associated with CD8+ T-cell activation. CONCLUSIONS: T-cell activation in patients on long-term successful ART is not due to residual low-level viral replication in the blood compartment of HIV-1. CD8+ T-cell activation in this patient group appears to be associated with poor CD4+ T-cell recovery.
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Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , ADP-Ribosil Ciclasa 1/análisis , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Carga Viral , Replicación Viral/efectos de los fármacosRESUMEN
BACKGROUND: HIV-1 infection is characterized by increase in inhibitory receptors and loss of activating receptors on natural killer (NK) cells, resulting in loss of cell activity. Exceptionally, for an inhibitory receptor, the proportion of NK cells bearing CD94-NKG2A decreases during HIV-1 infection. It is not understood whether HIV-1 itself or other concomitant infections drive these changes. OBJECTIVES: To investigate the relationship between HIV-1 viraemia and changes in C-type lectin-like receptor expression in NK cells and to investigate the effect of highly active antiretroviral therapy (HAART) on these changes. METHODS: Three cohorts of patients were studied: (1) before, during and after treatment interruption in aviraemic and viraemic patients receiving HAART (n = 15); (2) HIV-1-positive treatment-naive individuals (n = 13); and (3) HIV-1-positive individuals receiving successful HAART for a minimum of 1 year without interruption (n = 11). Flow cytometry was used to study the expression of NKG2A before and after treatment interruption and to define expanded populations of NK cells in untreated and treated HIV-1-positive individuals. Assays were performed in vitro to assess the cytotoxicity of the expanded populations. RESULTS: Increases in plasma HIV-1 RNA during treatment interruption in aviraemic HAART-treated individuals did not influence the proportion of NK cells carrying the complex CD94-NKG2A. Loss of NKG2A NK cells corresponded to the dramatic expansion of a distinct population of cells expressing a functional activating CD94-NKG2C receptor with skewed expression of killer cell immunoglobulin-like receptor family and natural cytotoxicity receptors. CONCLUSION: Changes in the NK cell repertoire during HIV-1 infection were not a result of HIV-1 viraemia alone but resembled those associated with concomitant infections.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Células Asesinas Naturales/metabolismo , Lectinas Tipo C/metabolismo , Viremia/metabolismo , Anticuerpos Antivirales/metabolismo , Estudios de Cohortes , Citometría de Flujo , Infecciones por VIH/inmunología , Humanos , Lectinas Tipo C/antagonistas & inhibidores , Persona de Mediana EdadAsunto(s)
Infecciones por VIH/inmunología , VIH-1 , ADP-Ribosil Ciclasa 1/biosíntesis , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Biomarcadores/análisis , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Infecciones por VIH/tratamiento farmacológico , Humanos , Factores Inmunológicos/uso terapéutico , Activación de Linfocitos , Control de Calidad , Resultado del TratamientoRESUMEN
Mucosal-associated invariant T (MAIT) cells are tissue-homing T cells recently implicated in HIV pathogenesis. We found that the proportion of MAIT cell in blood and colon of HIV+ patients are reduced in untreated infection. Antiretroviral therapy restored colonic but not blood MAIT cell percentages. We observed a negative correlation between colonic MAIT cells and T-cell activation in blood and suggest mucosal MAIT cell depletion may contribute to systemic immune activation in HIV infection.
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Antirretrovirales/uso terapéutico , Linfocitos T CD8-positivos/inmunología , Colon/inmunología , Infecciones por VIH/tratamiento farmacológico , Mucosa Intestinal/inmunología , Subfamilia B de Receptores Similares a Lectina de Células NK/análisis , Subgrupos de Linfocitos T/inmunología , Adulto , Linfocitos T CD8-positivos/química , Femenino , Infecciones por VIH/inmunología , Humanos , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/químicaRESUMEN
BACKGROUND: Lipopolysaccharide (LPS) is elevated in the plasma of individuals chronically infected with HIV-1 and is thought to contribute to chronic immune activation of myeloid cells and T-cells. Natural killer (NK) cells can also be stimulated by LPS in vitro. OBJECTIVES: To measure plasma LPS levels in individuals with HIV-1 infection, with or without suppressed plasma viral load, and in individuals with or without inflammatory bowel diseases (IBD). To compare the expression of NK cell receptors and activation markers in individuals with HIV-1 infection and in HIV-1-negative individuals with active IBD. METHODS: NK cells were studied by flow cytometry in treatment-naïve viraemic HIV-1-positive individuals (n = 14), aviraemic HIV-1-positive individuals (n = 19), HIV-1-negative individuals with inflammatory bowel disease (n = 10) and HIV-1-negative healthy control individuals (n = 17). Plasma endotoxin (LPS) was measured using the limulus amoebocyte assay. RESULTS: Viraemic and aviraemic HIV-1-positive individuals and patients with IBD have elevated levels of plasma LPS compared with HIV-1-negative individuals.HIV-1-positive individuals had significant changes in activation marker or NK cell receptor expression, whereas NK cells from IBD patients had similar levels to HIV-1-negative controls. NK cells from HIV-1-positive individuals are refractory to further stimulation by LPS in vitro. CONCLUSION: Elevated plasma LPS alone does not account for the chronic activation and receptor loss in NK cells from HIV-1-infected individuals.
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Infecciones por VIH/inmunología , VIH-1 , Células Asesinas Naturales/inmunología , Lipopolisacáridos/sangre , Activación de Linfocitos/inmunología , Adulto , Células Cultivadas , Infecciones por VIH/virología , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Persona de Mediana Edad , Receptores de Células Asesinas Naturales/sangre , Carga Viral , Adulto JovenRESUMEN
Invasive pneumococcal infection is an important cause of morbidity and mortality in HIV-1-infected individuals. B cells play an important role in maintaining serologic memory after infection. IgM memory B cells are significantly reduced in HIV-1-infected patients and their frequency is similar to that observed in other patient groups (splenectomized individuals and patients with primary Ab deficiency) who are also known to have an increased risk of invasive pneumococcal infection. Antiretroviral therapy does not restore marginal zone B cell percentages. Immunization with the 23-valent polysaccharide pneumococcal vaccine shows that HIV-1-infected patients have impaired total IgM and IgG pneumococcal vaccines compared with healthy controls. Loss of switched memory B cells was associated with impaired tetanus toxoid IgG vaccine responses. Results of this study demonstrate that defects in B cell memory subsets are associated with impaired humoral immune responses in HIV-1 patients who are receiving antiretroviral therapy and may be a contributory factor to the increased risk of invasive pneumococcal infection observed in HIV-1 infection.