Search

An individual’s T-cell repertoire constantly changes under the influence of external and internal factors. Cells that do not receive a stimulatory signal die, while those that encounter and recognize a pathogen or receive a co-stimulatory signal divide, resulting in clonal expansions. T-cell clones can be traced by monitoring the presence of their unique T-cell receptor (TCR) sequence, which is assembled de novo through a process known as V(D)J rearrangement. Tracking T cells can provide valuable insights into the survival of cells after hematopoietic stem cell transplantation (HSCT) or cancer treatment response and can indicate the induction of protective immunity by vaccination. In this study, we report a bioinformatic method for quantifying the T-cell repertoire dynamics from TCR sequencing data. We demonstrate its utility by measuring the T-cell repertoire stability in healthy donors, by quantifying the effect of donor lymphocyte infusion (DLI), and by tracking the fate of the different T-cell subsets in HSCT patients and the expansion of pathogen-specific clones in vaccinated individuals.

Abstract Background Lumbar disc degeneration (LDD) is a condition associated with recurrent low back pain (LBP). Knowledge regarding effective management is limited. As a step towards the identification of risk, prognostic or potentially modifiable factors in LDD patients, the aim of this study was to explore the hypothesis that intrinsic lumbar spine shape is associated with LDD and clinical outcomes in symptomatic adults. Methods 3 T MRI was used to acquire T2-weighted sagittal images (L1-S1) from 70 healthy controls and LDD patients (mean age 49 years, SD 11, range 31–71 years). Statistical Shape Modelling (SSM) was used to describe lumbar spine shape. SSM identified variations in lumbar shape as ‘modes’ of variation and quantified deviation from the mean. Intrinsic shape differences were determined between LDD groups using analysis of variance with post-hoc comparisons. The relationship between intrinsic shape and self-reported function, mental health and quality of life were also examined. Results The first 7 modes of variation explained 91% of variance in lumbar shape. Higher LDD sum scores correlated with a larger lumbar lordosis (Mode 1 (55% variance), P = 0.02), even lumbar curve distribution (Mode 2 (12% variance), P = 0.05), larger anterior-posterior (A-P) vertebral diameter (Mode 3 (10% variance), P = 0.007) and smaller L4-S1 disc spaces (Mode 7 (2% variance), P ≤ 0.001). In the presence of recurrent LBP, LDD was associated with a larger A-P vertebral diameter (Mode 3) and a more even lumbar curvature with smaller L5/S1 disc spaces (Mode 4), which was significantly associated with patient quality of life (P = 0.002–0.04, rp = 0.43–0.61)). Conclusions This exploratory study provides new evidence that intrinsic shape phenotypes are associated with LDD and quality of life in patients. Longitudinal studies are required to establish the potential role of these risk or prognostic shape phenotypes.

Abstract We aimed to examine whether back pain across adulthood was associated with spine shape at age 60–64 years. Data were from 1405 participants in the MRC National Survey of Health and Development, a nationally representative British birth cohort. Back pain was ascertained during nurse interviews at ages 36, 43, 53 and 60–64 years. Cumulative exposure to back pain was then derived by counting the number of ages at which back pain was reported. Statistical shape modelling was used to characterise thoracolumbar spine shape using lateral dual-energy x-ray absorptiometry images which were ascertained at age 60–64 years. Linear regression models were used to test associations of spine shape modes (SM) with: (1) cumulative exposure to back pain; (2) back pain reports during different periods of adulthood. After adjusting for sex, higher cumulative exposure to back pain across adulthood was associated with wedge-shaped L4-5 disc (lower SM4 scores) and smaller disc spaces (higher SM8 scores) in both sexes. In addition, reporting of back pain at ages 53 and/or 60–64 years was associated with smaller L4-5 disc space (lower SM6 scores) in men but not women. These findings suggest that back pain across adulthood may be associated with specific variations in spine shapes in early old age.

This study investigated associations between measures of adiposity from age 36 and spine shape at 60-64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60-64. Associations of spine shape modes with: 1) contemporaneous measures of total and central adiposity (body mass index (BMI), waist circumference (WC)) and body composition (android:gynoid fat mass ratio and lean and fat mass indices, calculated as whole body (excluding the head) lean or fat mass (kg) divided by height2 (m)2); 2) changes in total and central adiposity between age 36 and 60-64 and 3) age at onset of overweight, were tested using linear regression models. Four modes described 79% of the total variance in spine shape. In men, greater lean mass index was associated with a larger lordosis whereas greater fat mass index was associated with straighter spines. Greater current BMI was associated with a more uneven curvature in men and with larger anterior-posterior (a-p) vertebral diameters in both sexes. Greater WC and fat mass index were also associated with a-p diameter in both sexes. There was no clear evidence that gains in BMI and WC during earlier stages of adulthood were associated with spine shape but younger onset of overweight was associated with a more uneven spine and greater a-p diameter. In conclusion, sagittal spine shapes had different associations with total and central adiposity; earlier onset of overweight and prior measures of WC were particularly important.

Objective Lifting postures are frequently implicated in back pain. We previously related responses to a static load with intrinsic spine shape, and here we investigate the role of lumbar spine shape in lifting kinematics.Methods Thirty healthy adults (18–65 years) performed freestyle, stoop and squat lifts with a weighted box (6–15 kg, self-selected) while being recorded by Vicon motion capture. Internal spine shape was characterised using statistical shape modelling (SSM) from standing mid-sagittal MRIs. Associations were investigated between spine shapes quantified by SSM and peak flexion angles.Results Two SSM modes described variations in overall lumbar curvature (mode 1 (M1), 55% variance) and the evenness of curvature distribution (mode 2 (M2), 12% variance). M1 was associated with greater peak pelvis (r=0.38, p=0.04) and smaller knee flexion (r=–0.40, p=0.03) angles; individuals with greater curviness preferred to lift with a stooped lifting posture. This was confirmed by analysis of those individuals with very curvy or very straight spines (|M1|>1 SD). There were no associations between peak flexion angles and mode scores in stoop or squat trials (p>0.05). Peak flexion angles were positively correlated between freestyle and squat trials but not between freestyle and stoop or squat and stoop, indicating that individuals adjusted knee flexion while maintaining their preferred range of lumbar flexion and that ‘squatters’ adapted better to different techniques than ‘stoopers’.Conclusion Spinal curvature affects preferred lifting styles, and individuals with curvier spines adapt more easily to different lifting techniques. Lifting tasks may need to be tailored to an individual’s lumbar spine shape.