110 research outputs found
The Dynamics of T-Cell Receptor Repertoire Diversity Following Thymus Transplantation for DiGeorge Anomaly
T cell populations are regulated both by signals specific to the T-cell receptor
(TCR) and by signals and resources, such as cytokines and space, that act
independently of TCR specificity. Although it has been demonstrated that
disruption of either of these pathways has a profound effect on T-cell
development, we do not yet have an understanding of the dynamical interactions
of these pathways in their joint shaping of the T cell repertoire. Complete
DiGeorge Anomaly is a developmental abnormality that results in the failure of
the thymus to develop, absence of T cells, and profound immune deficiency. After
receiving thymic tissue grafts, patients suffering from DiGeorge anomaly develop
T cells derived from their own precursors but matured in the donor tissue. We
followed three DiGeorge patients after thymus transplantation to utilize the
remarkable opportunity these subjects provide to elucidate human T-cell
developmental regulation. Our goal is the determination of the respective roles
of TCR-specific vs. TCR-nonspecific regulatory signals in the growth of these
emerging T-cell populations. During the course of the study, we measured
peripheral blood T-cell concentrations, TCRÎČ V
gene-segment usage and CDR3-length spectratypes over two years or more for each
of the subjects. We find, through statistical analysis based on a novel
stochastic population-dynamic T-cell model, that the carrying capacity
corresponding to TCR-specific resources is approximately 1000-fold larger than
that of TCR-nonspecific resources, implying that the size of the peripheral
T-cell pool at steady state is determined almost entirely by TCR-nonspecific
mechanisms. Nevertheless, the diversity of the TCR repertoire depends crucially
on TCR-specific regulation. The estimated strength of this TCR-specific
regulation is sufficient to ensure rapid establishment of TCR repertoire
diversity in the early phase of T cell population growth, and to maintain TCR
repertoire diversity in the face of substantial clonal expansion-induced
perturbation from the steady state
Development of a Quantitative Bead Capture Assay for Soluble IL-7 Receptor Alpha in Human Plasma
IL-7 is an essential cytokine in T-cell development and homeostasis. It binds to the IL-7R receptor, a complex of the IL-7Rα (CD127) and common Îł (CD132) chains. There is significant interest in evaluating the expression of CD127 on human T-cells as it often decreased in medical conditions leading to lymphopenia. Previous reports showed the usefulness of CD127 as a prognostic marker in viral infections such as HIV, CMV, EBV and HCV. A soluble CD127 (sCD127) is released in plasma and may contribute to disease pathogenesis through its control on IL-7 activities. Measuring sCD127 is important to define its role and may complement existing markers used in lymphopenic disease management. We describe a new quantitative assay for the measurement of sCD127 in plasma and report sCD127 concentrations in healthy adults.We developed a quantitative bead-based sCD127 capture assay. Polyclonal CD127-specific antibodies were chosen for capture and a biotinylated monoclonal anti-CD127 antibody was selected for detection. The assay can detect native sCD127 and recombinant sCD127 which served as the calibrator. The analytical performance of the assay was characterized and the concentration and stability of plasma sCD127 in healthy adults was determined. The assay's range was 3.2â1000 ng/mL. The concentration of plasma sCD127 was 164±104 ng/mL with over a log variation between subjects. Individual sCD127 concentrations remained stable when measured serially during a period of up to one year.This is the first report on the quantification of plasma sCD127 in a population of healthy adults. Soluble CD127 plasma concentrations remained stable over time in a given individual and sCD127 immunoreactivity was resistant to repeated freeze-thaw cycles. This quantitative sCD127 assay is a valuable tool for defining the potential role of sCD127 in lymphopenic diseases
Clinical applications of immunoglobulin in neuromuscular diseases: focus on inflammatory myopathies
II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies
The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to CoffinâSiris syndrome
Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed CoffinâSiris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features
International Consensus Statement on Rhinology and Allergy: Rhinosinusitis
Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICARâRS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICARâRSâ2021 as well as updates to the original 140 topics. This executive summary consolidates the evidenceâbased findings of the document. Methods: ICARâRS presents over 180 topics in the forms of evidenceâbased reviews with recommendations (EBRRs), evidenceâbased reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICARâRSâ2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidenceâbased management algorithm is provided. Conclusion: This ICARâRSâ2021 executive summary provides a compilation of the evidenceâbased recommendations for medical and surgical treatment of the most common forms of RS
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