Prospective cohort study of Torque Teno Virus (TTV) viral load kinetics and the association with graft rejection in renal transplant patients.

INTRODUCTION: Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. MATERIALS AND METHODS: Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. RESULTS: Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881-0.9149, p < 0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p < 0.0001). Between (181-270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log10 copies/mL (by Home-Brew PCR) and 3.10 Log10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log10 copies/mL, respectively). CONCLUSIONS: Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period.

Allergen-specific CD4+ T cell responses in peripheral blood do not predict the early onset of clinical efficacy during grass pollen sublingual immunotherapy.

BACKGROUND: Surrogate biomarkers of efficacy are needed in support of allergen-specific immunotherapy. OBJECTIVE: The aim of this study was to relate changes in peripheral CD4(+) T cell responses to clinical efficacy during sublingual immunotherapy (SLIT). METHODS: Allergen-specific CD4(+) T cell responses were assessed in peripheral blood mononuclear cells (PBMCs) from 89 grass pollen-allergic individuals enrolled in a double-blind placebo-controlled SLIT study conducted in an allergen exposure chamber (ClinicalTrials.gov NCT00619827). Surface phenotype, proliferative responses, cytokine production and gene expression were analysed in coded samples at baseline, and after 2 and 4 months of SLIT, in PBMCs after in vitro allergen stimulation or among MHC class II/peptide (pMHCII)-tetramer-positive CD4(+) T cells. RESULTS: SLIT induced a 29.3% improvement of the average rhinoconjunctivitis total symptom score in the active group, when compared to the placebo group. In parallel, only minor changes in proportions of CD4(+) T cells expressing Th1 (CCR5(+), CXCR3(+)), Th2 (CRTh2(+), CCR4(+)) and Treg (CD25(+), CD127(-), Foxp3(+)) markers were detected. A down-regulation of IL-4 and IL-10 gene expression and IL-10 secretion (P < 0.001) were observed, as well as a decrease in the frequency of potential "pro-allergic" CD27(-) Th2 cells from patients receiving active tablets (P < 0.001), but without any correlation with clinical benefit. pMHCII-tetramer analyses failed to document any major impact in both numbers and polarization of circulating Phl p 1- and Phl p 5-specific CD4(+) T cells, confirming that early clinical improvement during SLIT is not associated with dramatic alterations in T lymphocyte responses. CONCLUSION & CLINICAL RELEVANCE: Changes in patterns of peripheral CD4(+) T cells are not markers for the early onset of efficacy during SLIT.

Changes in basophil activation during grass-pollen sublingual immunotherapy do not correlate with clinical efficacy.

BACKGROUND: Biomarkers predicting the safety and efficacy of sublingual immunotherapy (SLIT) remain to be established. METHODS: Eighty-nine patients with allergic rhinoconjunctivitis to grass pollen received either a placebo or five-grass-pollen daily tablet sublingually for 4 months. Following exposure in an allergen challenge chamber, clinical responders and nonresponders were identified individually by evaluating their rhinoconjunctivitis total symptom score (RTSS). Activation of peripheral blood basophils was measured by cytofluorometry before and after 2 or 4 months of immunotherapy, based on CD203c surface expression following allergen stimulation. RESULTS: Patients receiving the grass-pollen tablet had a relative mean improvement of 29.3% vs placebo in the average RTSS after 4 months of SLIT (P < 0.0003). No significant changes in basophil activation were noticed after 2 or 4 months of SLIT despite induction of specific IgGs. Among individual clinical responders, basophil activation was either decreased, increased, or unmodified during SLIT. Levels of basophil activation prior to immunotherapy were not predictive of local adverse reactions associated with immunotherapy. A moderate association was found between basophil activation and allergen-specific IgE levels, skin reactivity, or RTSS, suggesting that the former is, to some extent, indicative of disease severity. As such, patients with the highest level of basophil activation before treatment were more likely to benefit clinically from SLIT. CONCLUSIONS: Allergen reactivity of peripheral blood basophils is not a biomarker for adverse events or early onset of clinical responses to SLIT.

Patterns of use of oral anticancer treatments in France: a Retrospective Analysis of Cancer Treatments given ORally from 2004 to 2012 (Re-ACTOR study).

BACKGROUNDS AND OBJECTIVES: Increasing use of oral anticancer treatments (OATs) in oncology is modifying the treatment paradigm for cancer. Nonetheless, available data on the pattern of use of OATs and its evolution over time are limited. The objective of this study was to describe the patterns of use of OATs in France from 2004 to 2012. METHODS: A retrospective analysis was performed using Oncology Analyzer, a physician survey database. All patients actively treated by an oral or an intravenous anticancer treatment between October 2004 and September 2012 were enrolled in the database. Descriptive analyses were performed by treatment category with a focus on the last year of collection and the evolution across the study period. RESULTS: From October 2011 to September 2012, a sample of 7426 patients treated by oral or intravenous active anticancer treatments was analyzed: 74% of patients receiving an OAT were diagnosed with a solid tumor, 52% of whom had a stage IV cancer. The use of OATs increased with age and was the highest in patients over 80 years. From 2004 to 2012, the proportion of cancer patients receiving OATs increased by four percentage points (from 28.4% to 32.5%). Additionally, for treatments available in both forms, a marked preference for oral formulations was observed. LIMITATIONS: The patterns and trend of use prior to 2004 were not addressed due to lack of information in the database. The use of a market research database is relevant for highly prevalent cancers but for rare cancers the sample size is limited, underlining the utility of using other data sources such as cancer registries. CONCLUSIONS: The Re-ACTOR study provides an overview of OAT use in France, which was prescribed to 32% of cancer patients in France in 2012, principally to older patients and to those with solid tumors and with metastatic disease.

Chlamydia trachomatis en las infecciones respiratorias agudas del tracto inferior en menores de 6 meses / Chlamydia trachomatis in low tract acute respiratory infections in infants under 6 months of age

En este trabajo retrospectivo se presentan los resultados de serología para Chlamydia trachomatis, de detección de sus antígenos así como de infecciones mixtas a virus y clamidia en niños menores de 6 meses con neumonía o bronquiolitis internados en hospitales públicos de Buenos Aires. Se estudiaron 297 sueros pertenecientes a dos poblaciones: a) niños con etiología viral y bacteriana negativa y b) niños en los que no se excluyó previamente etiología viral ni bacteriana. Los anticuerpos anti-C. trachomatis (IgG e IgM) se investigaron por enzimoinmunoensayo (EIE), microinmunofluorescencia (MIF) y/o inmunofluorescencia indirecta (IFI). En 145 aspirados nasofaríngeos (ANF) se investigó Virus Sincicial Respiratorio (RSV) y Adenovirus por IFI. En 25 pacientes con diagnóstico de infección reciente por clamidia se determinó antígeno clamidial en el ANF por EIE. Se determinó la presencia de infección reciente por C. trachomatis en el 15 por ciento de los casos (45/297) mediante la detección de IgM específica, seroconversión para IgG en muestras pareadas y/o títulos elevados y estables de IgG. El 29,6 por ciento de los pacientes presentó IgG (88/297). La frecuencia de infección reciente en las dos poblaciones de niños fue similar. En neumonías se registró una frecuencia significativamente mayor de infección reciente por C. trachomatis (24,3 por ciento) que en bronquiolitis (11,6 por ciento) (p<0,007). En el 40 por ciento de los pacientes con infección reciente por C. trachomatis (10/25) se pudo demostrar la presencia de antígeno clamidial en ANF. El 62 por ciento de los niños con infección reciente fueron menores de 2 meses de edad. En el análisis de las historias clínicas no se observaron diferencias significativas entre los niños con infección reciente por C. trachomatis versus los que presentaron diagnóstico negativo. Se detectó RSV en el 37 por ciento de los casos estudiados, Adenovirus en el 4 por ciento e infección mixta RSV-clamidia en el 5,5 por ciento. Estos resultados señalan la importancia en nuestro medio de C. trachomatis en las neumonías y bronquiolitis en menores de 6 meses y sugiere la necesidad de su diagnóstico rápido para instituir el tratamiento específico.