RESUMEN
The immunopathophysiological mechanisms underlying chronic inflammatory demyelinating polyneuropathy (CIDP) in an individual patient are largely unknown. Better understanding of these mechanisms may aid development of biomarkers and targeted therapies. Both B- and T-cell dominant mechanisms have been implicated. We therefore investigated whether B-cell and T-cell receptor (BCR/TCR) repertoires might function as immunological biomarkers in CIDP. In this prospective cohort study, we longitudinally sampled peripheral blood of CIDP patients in three different phases of CIDP: starting induction treatment (IT), starting withdrawal from IVIg maintenance treatment (MT), and patients in remission (R). BCR and TCR repertoires were analyzed using RNA based high throughput sequencing. In baseline samples, the number of total clones, the number of dominant BCR and TCR clones and their impact on the repertoire was similar for patients in the IT, MT, and remission groups compared with healthy controls. Baseline samples in the IT or MT did not predict treatment response or potential relapse at follow-up. Treatment responders in the IT group showed a potential IVIg-induced increase in the number of dominant BCR clones and their impact at follow-up (baseline1.0 [IQR 1.0-2.8] vs. 6 m 3.5 [0.3-6.8]; P < .05, Wilcoxon test). Although the BCR repertoire changed over time, the TCR repertoire remained robustly stable. We conclude that TCR and BCR repertoire distributions do not predict disease activity, treatment response or response to treatment withdrawal.
Asunto(s)
Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Humanos , Inmunoglobulinas Intravenosas , Estudios Prospectivos , Biomarcadores , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
OBJECTIVES: An important limitation in granulomatosis with polyangiitis (GPA) is the lack of disease activity markers. Immunoglobulin G4-positive (IgG4+) B cells and plasma cells are implicated in the pathogenesis of GPA. We hypothesized that the presence of these cells in peripheral blood could serve as disease activity parameter in GPA. METHODS: We included 35 proteinase 3-antineutrophil cytoplasmic antibodies-positive patients with GPA in a cross-sectional study. Active disease was defined as Birmingham Vasculitis Activity Score (BVAS) ≥ 3 (n = 15), remission as BVAS of 0 (n = 17), and low disease activity (LDA) as BVAS of 1-2 and clinical remission (n = 3). Healthy subjects (n = 10), patients with systemic lupus erythematosus (n = 24), and patients with rheumatoid arthritis (n = 19) functioned as control subjects. An additional longitudinal study was performed in ten patients with GPA. Using a validated qPCR test, we measured the IgG4:IgG RNA ratio in all groups and compared the results with known biomarkers. RESULTS: The median qPCR score was higher in active GPA (21.4; IQR 12.1-29.6) than in remission/LDA (3.3; IQR 1.6-5.6) (Mann-Whitney U test, p < 0.0001) and outperformed other known disease activity parameters in detecting activity. A cutoff qPCR score of 11.2% differentiated active disease from remission/LDA accurately (AUC 0.993). The qPCR test correlated well with the BVAS (Spearman r = 0.77, p < 0.0001). In the longitudinal study, a decrease in BVAS correlated with qPCR score reduction (paired t test, p < 0.05). CONCLUSIONS: The IgG4:IgG RNA ratio in GPA accurately distinguishes active disease from remission and correlates well with disease activity in these single-center studies. If these results are confirmed in larger longitudinal studies, this test might help to steer treatment decisions in patients with GPA.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Linfocitos B/inmunología , Granulomatosis con Poliangitis/diagnóstico , Inmunoglobulina G/genética , Mieloblastina/inmunología , Células Plasmáticas/inmunología , ARN/genética , Adulto , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Linfocitos B/metabolismo , Biomarcadores/sangre , Estudios Transversales , Diagnóstico Diferencial , Femenino , Granulomatosis con Poliangitis/genética , Granulomatosis con Poliangitis/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mieloblastina/metabolismo , Células Plasmáticas/metabolismo , ARN/sangre , ARN/inmunología , Remisión Espontánea , Adulto JovenRESUMEN
The endothelium is crucially important for the delivery of oxygen and nutrients throughout the body under homeostatic conditions. However, it also contributes to pathology, including the initiation and perpetuation of inflammation. Understanding the function of endothelial cells (ECs) in inflammatory diseases and molecular mechanisms involved may lead to novel approaches to dampen inflammation and restore homeostasis. In this article, we discuss the various functions of ECs in inflammation with a focus on pathological angiogenesis, attraction of immune cells, antigen presentation, immunoregulatory properties and endothelial-to-mesenchymal transition (EndMT). We also review the current literature on approaches to target these processes in ECs to modulate immune responses and advance anti-inflammatory therapies.
Asunto(s)
Células Endoteliales/fisiología , Neovascularización Patológica/inmunología , Animales , Efecto Espectador , Citocinas/fisiología , Transición Epitelial-Mesenquimal , Humanos , Inmunidad Celular , Inmunidad Innata , Inflamación/inmunología , Inflamación/patología , Neovascularización Patológica/patología , Transducción de SeñalRESUMEN
N-type metal oxide solar cells sensitized by infrared absorbing PbS quantum dots (QDs) represent a promising alternative to traditional photovoltaic devices. However, colloidal PbS QDs capped with pure organic ligand shells suffer from surface oxidation that affects the long term stability of the cells. Application of a passivating CdS shell guarantees the increased long term stability of PbS QDs, but can negatively affect photoinduced charge transfer from the QD to the oxide and the resulting photoconversion efficiency (PCE). For this reason, the characterization of electron injection rates in these systems is very important, yet has never been reported. Here we investigate the photoelectron transfer rate from PbS@CdS core@shell QDs to wide bandgap semiconducting mesoporous films using photoluminescence (PL) lifetime spectroscopy. The different electron affinity of the oxides (SiO2, TiO2 and SnO2), the core size and the shell thickness allow us to fine tune the electron injection rate by determining the width and height of the energy barrier for tunneling from the core to the oxide. Theoretical modeling using the semi-classical approximation provides an estimate for the escape time of an electron from the QD 1S state, in good agreement with experiments. The results demonstrate the possibility of obtaining fast charge injection in near infrared (NIR) QDs stabilized by an external shell (injection rates in the range of 110-250 ns for TiO2 films and in the range of 100-170 ns for SnO2 films for PbS cores with diameters in the 3-4.2 nm range and shell thickness around 0.3 nm), with the aim of providing viable solutions to the stability issues typical of NIR QDs capped with pure organic ligand shells.
RESUMEN
We report the observation of unintentionally incorporated nitrogen-related complexes in ZnO and GaN nanowires grown by the catalytic vapor-phase transport method. In particular, our experimental findings from Raman scattering spectroscopy and mass-selected time-of-flight particle emission measurements suggest the presence of interstitial nitrogen molecules that are formed during the nanowire growth. These results may be relevant for many nanowire systems, emphasizing the necessity of more studies on unintentional impurity incorporations in these nanomaterials.