Glucosylsphingosine is a reliable response biomarker in <scp>G</scp>aucher disease

Arkadir, David; Dinur, Tama; Revel‐Vilk, Shoshana; Cohen, Michal Becker; Cozma, Claudia; Hovakimyan, Marina; Eichler, Sabrina; Rolfs, Arndt; Zimran, Ari

doi:10.1002/ajh.25074

Cited by 33 publications

(39 citation statements)

References 6 publications

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“…Using the NICE STA method, risk of bias in the sole randomized controlled trial was deemed low, although bias regarding the allocation concealment process and between-group baseline similarities was unclear ( Table S1 ) [ 36 ]. Thirty non-randomized clinical trials and observational studies with full-study reporting were assessed using the Newcastle–Ottawa scoring tool [ 3 , 26 , 33 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ], of which 19 were deemed to have a high risk of bias (score 0–3; Table S2 ). Thirty-two animal studies were assessed using the SYRCLE risk of bias tool [ 45 , 53 , 58 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , …”

Section: Resultsmentioning

confidence: 99%

“…In 17 studies, cross-sectional and longitudinal data on lyso-Gb1 in treated and untreated patients with GD were compared [ 33 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. Results from 16 of the 17 studies showed that treatment with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) either alone or in combination produced marked reductions in lyso-Gb1 concentrations in plasma, cerebrospinal fluid (CSF), and urine relative to baseline or control ( Table S6 ).…”

Section: Resultsmentioning

confidence: 99%

“…Similar findings were observed after the initiation of SRT [ 43 ]. A retrospective analysis of 25 non-splenectomized patients with GD homozygous for the non-neuronopathic N370S GBA mutation in the GBA1 gene who received low-dose ERT (15 units/kg/month) revealed an exponential decay (Pearson product moment determination coefficient ( r 2 ), 0.84) in lyso-Gb1 plasma over 72 months [ 37 ]. ERT also lowered lyso-Gb1 content in RBC membranes in a prospective, multicenter, cross-sectional, case-control study of 15 patients with type 1 and neuronopathic GD receiving ERT versus 16 untreated counterparts [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

“…Ten of the 17 studies provided different evidence levels of information on lyso-Gb1 as a response biomarker in GD ( Table 6 ) [ 36 , 37 , 38 , 39 , 40 , 43 , 44 , 47 , 49 , 51 ]. The results of a prospective, multicenter, cross-sectional, case-control study in treatment-naïve and splenectomized patients with type 1 GD showed that lyso-Gb1 concentrations in plasma (Pearson product moment correlation coefficient ( r ), –0.83) and RBC membranes (−0.65) correlated inversely with hematocrit [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

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Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review

Revel‐Vilk

Fuller

Zimran

2020

IJMS

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The challenges in the diagnosis, prognosis, and monitoring of Gaucher disease (GD), an autosomal recessive inborn error of glycosphingolipid metabolism, can negatively impact clinical outcomes. This systematic literature review evaluated the value of glucosylsphingosine (lyso-Gb1), as the most reliable biomarker currently available for the diagnosis, prognosis, and disease/treatment monitoring of patients with GD. Literature searches were conducted using MEDLINE, Embase, PubMed, ScienceOpen, Science.gov, Biological Abstracts, and Sci-Hub to identify original research articles relevant to lyso-Gb1 and GD published before March 2019. Seventy-four articles met the inclusion criteria, encompassing 56 related to pathology and 21 related to clinical biomarkers. Evidence for lyso-Gb1 as a pathogenic mediator of GD was unequivocal, although its precise role requires further elucidation. Lyso-Gb1 was deemed a statistically reliable diagnostic and pharmacodynamic biomarker in GD. Evidence supports lyso-Gb1 as a disease-monitoring biomarker for GD, and some evidence supports lyso-Gb1 as a prognostic biomarker, but further study is required. Lyso-Gb1 meets the criteria for a biomarker as it is easily accessible and reliably quantifiable in plasma and dried blood spots, enables the elucidation of GD molecular pathogenesis, is diagnostically valuable, and reflects therapeutic responses. Evidentiary standards appropriate for verifying inter-laboratory lyso-Gb1 concentrations in plasma and in other anatomical sites are needed.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review

Revel‐Vilk

Fuller

Zimran

2020

IJMS

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“…Explaining this lack of correlation with GD has been difficult. Although glucosylsphingosine seem implicated in the pathogenesis and has been found a reliable biomarker of GD activity, the association between the level of glucosylsphingosine and risk of PG and/or MG is still unclear [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin Abnormalities in Gaucher Disease: an Analysis of 278 Patients Included in the French Gaucher Disease Registry

Nguyen

Stirnemann

Lautredoux

et al. 2020

IJMS

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Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40–9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.

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