Gaucher disease (GD) leads to accumulation of glucosylceramide (GL1) and its deacylated lysolipid, glucosylsphingosine (lyso-GL1) which is implicated in mediating immune dysregulation and skeletal disease. The aim of our study was to assess plasma Lyso-GL1 as a biomarker of GD and its response to therapy.
Plasma lyso-GL1 in 169 patients with GD type 1 (GD1) was measured by LC-MS/MS. Significant predictors of were assessed by Pearson’s correlation coefficient, Wilcoxon Mann Whitney test and multiple linear regression. Propensity scores were used to match patients on treatment mode: Enzyme Replacement Therapy (ERT) vs Eliglustat Tartrate SRT (ELI-SRT).
Lyso-GL1 levels in healthy controls on average was 1.5 ng/ml (1.3 – 1.7; 95% CI). In untreated GD patients, the levels were massively elevated (180.9 ng/ml: 95% CI, 145.4 – 216.5) and ERT resulted in marked reduction (89 ng/ml: 95% CI, 69.2 – 129.4) (p<0.001). Lyso-GL1 correlated with chitotriosidase (r=0.59 p<0.001), CCL18 (r= 0.62 p <0.001), hepatomegaly (r=0.28 p<0.001), splenomegaly (r=0.27 p=0.003), splenectomy (p=0.01) and treatment mode (p<0.001). By multiple linear regression, the strongest predictors of lyso-GL1 were age (p<0.001), splenectomy (p=0.02), Chitotriosidase (p<0.001) and CCL18 levels (p=0.001). After propensity score matching to obtain comparable groups of patients on ERT vs ELI-SRT, lyso-GL1 levels were lower among patients receiving ELI-SRT by 113 ng/ml (95% CI: 136 – 90.3 ng/ml p<0.001).
Plasma lyso-GL1 is a key biomarker of GD. ERT reduced lyso-GL1 levels. By propensity scoring, ELI-SRT resulted in greater reduction of lyso-GL1 than ERT.
We have developed a CT scoring system that is both sensitive and specific for the diagnosis of NSTIs. This system may allow clinicians to more accurately diagnose NSTIs. Prospective validation of this scoring system is planned.
In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms.
This systematic evaluation showed that there is a very high degree of agreement between diagnostic findings assessed on 3D-TSE and conventional 2D-FSE sequences. Overall, intermethod agreement was statistically noninferior to the intraobserver agreement between repeated 2D-FSE evaluations. Overall, this study shows that 3D-TSE performs equivalently, if not superiorly to 2D-FSE sequences. Reviewers found particular utility for the ability to manipulate image planes with the 3D-TSE if there was greater pathology or anatomic variation.
There is a high degree of agreement between 3D-TSE and 2D-FSE MRI in assessing the cervical spine. The intermethod variability was statistically similar to the intrinsic intrarater variability of 2D-FSE MRI. This study demonstrates that 3D-TSE yields at least equivalent diagnostic information as conventional 2D-FSE in the cervical spine. In addition, reviewers noted subjective advantages of 3D-TSE image reprocessing, especially when evaluating greater pathology or deformity, with a simplified image acquisition process.
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