Plasma chitotriosidase activity versus CCL18 level for assessing type I Gaucher disease severity: protocol for a systematic review with meta-analysis of individual participant data

Abstract

BackgroundGaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by deficiency in acid beta-glucosidase. GD exhibits a wide clinical spectrum of disease severity with an unpredictable natural course. Plasma chitotriosidase activity and CC chemokine ligand 18 (CCL18) have been exchangeably used for monitoring GD activity and response to enzyme replacement therapy in conjunction with clinical assessment. Yet, a large-scale head-to-head comparison of these two biomarkers is currently lacking. We propose a collaborative systematic review with meta-analysis of individual participant data (IPD) to compare the accuracy of plasma chitotriosidase activity and CCL18 in assessing type I (i.e., non-neuropathic) GD severity.MethodsEligible studies include cross-sectional, cohort, and randomized controlled studies recording both plasma chitotriosidase activity and CCL18 level at baseline and/or at follow-up in consecutive children or adult patients with type I GD. Pre-specified surrogate outcomes reflecting GD activity include liver and spleen volume, hemoglobin concentration, platelet count, and symptomatic bone events with imaging confirmation. Primary studies will be identified by searching Medline (1995 onwards), EMBASE (1995 onwards), and Cochrane Central Register of Controlled Trials (CENTRAL). Electronic search will be complemented by contacting research groups in order to identify unpublished relevant studies. Where possible, IPD will be extracted from published articles. Corresponding authors will be invited to collaborate by supplying IPD. The methodological quality of retrieved studies will be appraised for each study outcome, using a checklist adapted from the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcome will be a composite of liver volume >1.25 multiple of normal (MN), spleen volume >5 MN, hemoglobin concentration <11 g/dL, or platelet count <100 × 109/L. Effect size estimates for biomarker comparative accuracy in predicting outcomes will be reported as differences in areas under receiver operating characteristic curves along with 95% confidence intervals. Effect size estimates will be reported as (weighted) mean differences along with 95% confidence intervals for each biomarker according to outcomes. IPD meta-analysis will be conducted with both one- and two-stage approaches.DiscussionValid and precise accuracy estimates will be derived for CCL18 relative to plasma chitotriosidase activity in discriminating patients according to GD severity.Systematic review registrationPROSPERO 2015 CRD42015027243 Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-017-0483-x) contains supplementary material, which is available to authorized users.

Gaucher disease and SARS-CoV-2 infection: Emerging management challenges

“…Similar therapeutic effects are obtained by oral substrate reduction therapy (SRT) using inhibitors of glucosylceramide synthase [40]. Monitoring of selected cytokine/chemokines have been explored as "biomarkers" for effectiveness and progress of ERT [41,42]. Chitotriosidase, a marker of alternatively activated macrophages and lyso-Gb1, the accumulating bioactive lipid, are important biomarkers of GD severity and response to therapy [43].…”

Hepato- and splenomegaly in selected metabolic diseases – diagnostics and differentiation

“…Powiększenie zarówno wątroby, jak i śledziony występuje, gdy proces spichrzania dotyczy makrofagów układu siateczkowo-śródbłonkowego [1][2][3][12][13][14]. Komórki Browicz-Kupffera również pochodzą z układu fagocytarnego i stanowią największy rezerwuar makrofagów człowieka.…”

“…Makrofagi fagocytują rozpadłe elementy morfotyczne krwi, bogate w błony (membrany), dlatego aktywność chitotriozydazy wzrasta w lizosomalnych chorobach spichrzeniowych, takich jak choroba Gauchera czy Niemanna-Picka. Należy jednak pamiętać, że u ok. 6% populacji rasy kaukaskiej jest on zupełnie nieaktywny z powodu homozygotyczności dla częstej mutacji 24bp w genie CHIT [12][13][14].…”

YKL-39 as a Potential New Target for Anti-Angiogenic Therapy in Cancer

“…AMCase is induced by IL-13 and is found in allergic inflammations such as asthma (8,9). Chitotriosidase is expressed by phagocytic cells and is a biomarker for Gaucher's disease, a lysosomal storage disease that involves the dysfunctional metabolism of sphingolipids (10,11).…”