Characterization of the domestic goat γδ T cell receptor gene loci and gene usage

Abstract

Background Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. Methods We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London). Findings 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43•2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0•77 [95% CI 0•76 to 0•78]; calibration-in-the-large 0•00 [-0•05 to 0•05]); calibration slope 0•96 [0•91 to 1•01]), and greater net benefit than any other reproducible prognostic model. Interpretation The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19.

The Organization of the Pig T-Cell Receptor γ (TRG) Locus Provides Insights into the Evolutionary Patterns of the TRG Genes across Cetartiodactyla

“…Its preservation for such a long evolutionary time, implies a highly specialized function of its genes, which could be essential for the survival of the species. For instance, it has been shown that the genes within the TRGC5 cassette would preferentially be expressed in specific γδ cell populations in pigs as well as in ruminants [ 39 , 45 ].…”

The Organization of the Pig T-cell Receptor Gamma (TRG) Locus Provides Insights Into the Evolutionary Patterns of the TRG Genes Across Cetartiodactyla

“…Its preservation for such a long evolutionary time, implies a highly specialized function of its genes, which could be essential for the survival of the species. For instance, it has been shown that the genes within the TRGC5 cassette would preferentially be expressed in specific gd cell populations in pigs as well as in ruminants [39,45].…”

Surfing on the waves of the human γδ T cell ontogenic sea

“…43 Conversely, αβ T cells become prevalent in the thymus around 10 PCW, while the first naive αβ T cells egress the gland and migrate toward the periphery around 11 or 12 PCW. 43 Even-toed ungulates (Artiodactyla), which include several TCR γδ high (γδ-hi) species such as pig and goat, 30,45,46 appear to follow an "early" pattern of γδ thymocyte wave like in human (Figure 1), achieving adult-like levels of γδ thymocytes and a diverse TCR repertoire before birth. [46][47][48] Intriguingly, even though γδ-hi species possess high levels of γδ T cells in the periphery during mid-late gestation and the first year of life, the proportion of γδ thymocytes remains relatively low than their conventional αβ counterparts 30,49 (Figure 1).…”