Elevated Syndecan-1 Research Articles

Endothelial injury and decline in lung function in persons living with HIV: a prospective Danish cohort study including 698 adults.

Endothelial injury may promote declining lung function. We aimed to investigate in well-treated persons living with HIV (PLWH) whether elevated levels of thrombomodulin (TM) and syndecan-1 (SDC1) are associated with excess lung function decline and worsening dyspnea. A prospective cohort study comprising patients from the Copenhagen municipality. We included 698 PLWH with undetectable viral load. Biomarkers and demographics were measured at baseline, spirometry [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] and dyspnea score both at baseline and 2-year follow-up.Both biomarkers were dichotomized at the 3rd quartile. Decline in lung function was estimated using a linear mixed model with patient-specific random effect. Increase in dyspnea score was estimated using a general mixed logistic regression model. We did not find an association between elevated SDC1 or TM and an excess decline in neither FEV1: SDC1: 4.5 mL/year (95% CI: -3.9-12.9, p = 0.30), TM: 2.2 mL/year (95% CI: -6.0-10.4, p = 0.60) nor FVC: SDC1: 4.1 mL/year (95% CI: -6.0-14.2, p = 0.42), TM: 1.4 mL/year (95% CI: -8.3-11.1, p = 0.78). A subgroup analysis of never-smokers was consistent with the main analysis.Likewise, we did not find any association between elevated SDC1 and TM and increase in dyspnea score: SDC1: OR 1.43 (95% CI: 0.89-2.30, p = 0.14), TM: OR 1.05 (95% CI: 0.65-1.71, p = 0.26). We did not find a significant association between elevated biomarkers of endothelial injury and decline in lung function nor dyspnea.

Endotheliopathy of trauma in children: The association of syndecan-1 with injury and poor outcomes.

The contribution of the endothelium to trauma-induced coagulopathy has not been thoroughly investigated in injured children. This is a prospective cohort study of children (younger than 18 years) who presented with a potentially severe injury to an academic pediatric trauma center. Syndecan-1 level was collected on arrival and 24 hours following hospital arrival. Children were categorized as injured versus uninjured based on results of trauma evaluation. Demographics, injury characteristics, vital signs, and clinical laboratories were recorded. A composite clinical outcome was defined as death or blood product transfusion within 24 hours of hospital arrival. Statistical tests determined the impact of injury characteristics and therapeutics on syndecan-1 levels and assessed for associations between syndecan-1 level and outcomes. A total of 121 subjects were included in the analysis: 96 injured (79%) and 25 uninjured (21%). There were no differences between groups in age (median [interquartile range (IQR)], 11 [4-14] years), sex, or race. The injured cohort had a median (IQR) Injury Severity Score of 16 (9-21), 75% had blunt mechanism, 26% were transfused within 6 hours, 3% had 24-hour mortality, and 6% had in-hospital mortality. Median (IQR) syndecan-1 level on admission was significantly higher in injured versus uninjured cohort (44 [21-75] vs. 25 [17-42]; p = 0.04). Admission base deficit was significantly correlated with syndecan-1 level ( r = 0.8, p < 0.001); no association with traumatic brain injury or injury mechanism was seen. Children with elevated syndecan-1 on admission had significantly increased odds of poor outcome; every 10 ng/mL increase in syndecan-1 was associated with 10% increased odds of death or transfusion ( p < 0.001). Transfusion with any blood product was associated with a significant decrease in syndecan-1 from arrival to 24 hours (Δ syndecan-1, -17 [-64 to -5] vs. -8 [-19 to +2]; p < 0001). Elevated admission syndecan-1 level, suggestive of endotheliopathy, was associated with shock and poor outcomes in pediatric trauma. Larger cohort studies are required to fully describe the complexities of trauma-induced coagulopathy and investigate the benefit of therapies targeting endotheliopathy in children. Prognostic and Epidemiological; Level III.

Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids.

To assess the disruption of endothelial glycocalyx integrity in children with sepsis receiving fluid resuscitation with either balanced or unbalanced crystalloids. The primary outcome was endothelial glycocalyx disruption (using perfused boundary region >2 µm on sublingual video microscopy and syndecan-1 greater than 80 mg/dL) according to the type of crystalloid. The secondary outcomes were increased vascular permeability (using angiopoietin-2 level), apoptosis (using annexin A5 level), and associated clinical changes. A single-center prospective cohort study from January to December 2021. Twelve medical-surgical PICU beds at a university hospital. Children with sepsis/septic shock before and after receiving fluid resuscitation with crystalloids for hemodynamic instability. None. We included 106 patients (3.9 yr [interquartile range, 0.60-13.10 yr]); 58 of 106 (55%) received boluses of unbalanced crystalloid. This group had greater odds of endothelial glycocalyx degradation (84.5% vs 60.4%; adjusted odds ratio, 3.78; 95% CI, 1.49-9.58; p < 0.01) 6 hours after fluid administration, which correlated with increased angiopoietin-2 (rho = 0.4; p < 0.05) and elevated annexin A5 ( p = 0.04). This group also had greater odds of metabolic acidosis associated with elevated syndecan-1 (odds ratio [OR], 4.88; 95% CI, 1.23-28.08) and acute kidney injury (OR, 1.7; 95% CI, 1.12-3.18) associated with endothelial glycocalyx damage. The perfused boundary region returned to baseline 24 hours after receiving the crystalloid boluses. Children with sepsis, particularly those who receive unbalanced crystalloid solutions during resuscitation, show loss and worsening of endothelial glycocalyx. The abnormality peaks at around 6 hours after fluid administration and is associated with greater odds of metabolic acidosis and acute kidney injury.

INTESTINAL DAMAGE AND IMMUNE RESPONSE AFTER EXPERIMENTAL BLUNT ABDOMINAL TRAUMA

Abdominal trauma (AT) is of major global importance, particularly because the civil, terroristic, and military traumatic potential of blast injuries has increased. The consequences of blunt abdominal injuries are highly variable and frequently underestimated or even overlooked. However, the underlying path mechanisms and subsequent innate immune response remain poorly understood. Therefore, we investigated the spatiotemporal local and systemic effects of a standardized blast-induced blunt AT on the intestine and innate immune response. In an established AT model, 66 male C57Bl6 mice were anesthetized and exposed to either a single blast wave centered on the epigastrium or control treatment (sham). At 2, 6, or 24 hours after trauma induction, animals were sacrificed. In 16 of 44 (36%) AT animals, one or more macroscopically visible injuries of the intestine were observed. Epithelial damage was detected by histological analysis of jejunum and ileum tissue samples, quantified by the Chiu score and by increased plasma concentrations of the intestinal fatty acid-binding protein, an enterocyte damage marker. Moreover, in the early posttraumatic period, elevated syndecan-1, claudin-5, and mucin-2 plasma levels also indicated alterations in the gut-blood barrier. Increased levels of pro-inflammatory cytokines such as TNF and macrophage inflammatory protein 2 in tissue homogenates and plasma indicate a systemic immune activation after blunt AT. In conclusion, we detected early morphological intestinal damage associated with high, early detectable intestinal fatty acid-binding protein plasma levels, and a considerable time- and dose-dependent impairment of the gut-blood barrier in a newly established mouse model of blunt AT. It appears to be a sufficient model for further studies of the intestinal immunopathophysiological consequences of AT and the evaluation of novel therapeutic approaches.

TRAUMA-DERIVED EXTRACELLULAR VESICLES ARE SUFFICIENT TO INDUCE ENDOTHELIAL DYSFUNCTION AND COAGULOPATHY.

Although a number of studies have demonstrated increased release of extracellular vesicles (EVs) and changes in their origin differentials after trauma, the biologic significance of EVs is not well understood. We hypothesized that EVs released after trauma/hemorrhagic shock (HS) contribute to endotheliopathy and coagulopathy. To test this hypothesis, adoptive transfer experiments were performed to determine whether EVs derived from severely injured patients in shock were sufficient to induce endothelial dysfunction and coagulopathy. Methods: Total EVs were enriched from plasma of severely injured trauma/HS patients or minimally injured patients by ultracentrifugation and characterized for size and numbers. Under isoflurane anesthesia, noninjured naive C57BL/6J mice were administered EVs at varying concentrations and compared with mice receiving equal volume vehicle (phosphate-buffered saline (PBS)) or to mice receiving EVs from minimally injured patients. Thirty minutes after injection, mice were sacrificed, and blood was collected for thrombin generation (thrombin-antithrombin, thrombin-antithrombin complex [TAT] assay) and syndecan-1 by enzyme-linked immunoabsorbent assay (ELISA). Lungs were harvested for examination of histopathologic injury and costained with von Willebrand factor and fibrin to identify intravascular coagulation. Bronchial alveolar lavage fluid was aspirated from lungs for protein measurement as an indicator of the endothelial permeability. Data are presented as mean ± SD, P < 0.05 was considered significant, and t test was used. Results: An initial proof-of-concept experiment was performed in naive mice receiving EVs purified from severely injured trauma/HS patients (Injury Severity Score [ISS], 34 ± 7) at different concentrations (5 × 106 to 3.1 × 109/100 μL/mouse) and compared with PBS (control) mice. Neither TAT nor syndecan-1 levels were significantly different between groups at 30 minutes after EV infusion. However, lung vascular permeability and histopathologic injury were significantly higher in the EV group, and lung tissues demonstrated intravascular fibrin deposition. Based on these data, EVs from severely injured trauma/HS patients (ISS, 32 ± 6) or EVs from minimally injured patients (ISS, 8 ± 3) were administered to naive mice at higher concentrations (1 × 109 to 1 × 1010 EV/100 μL/mouse). Compared with mice receiving EVs from minimally injured patients, plasma TAT and syndecan-1 levels were significantly higher in the trauma/HS EV group. Similarly, bronchial alveolar lavage protein and lung histopathologic injury were higher in the trauma/HS EV group, and lung tissues demonstrated enhanced intravascular fibrin deposition. Conclusion: These data demonstrate that trauma/HS results in the systemic release of EVs, which are capable of inducing endotheliopathy as demonstrated by elevated syndecan-1 and increased permeability and coagulopathy as demonstrated by increased TAT and intravascular fibrin deposition. Targeting trauma-induced EVs may represent a novel therapeutic strategy.

Biomarkers of Glycocalyx Injury and Endothelial Activation are Associated with Clinical Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis.

Sepsis is one of the main causes of morbidity and mortality worldwide. Microcirculatory impairment, especially damage to the endothelium and glycocalyx, is often not assessed. The objective of this systematic review and meta-analysis was to summarize the available evidence of the risk of unsatisfactory outcomes in patients with sepsis and elevated glycocalyx injury and endothelial activation biomarkers. A systematic search was carried out on PubMed/MEDLINE, Embase, Cochrane and Google Scholar up to December 31, 2021, including studies in adults and children with sepsis which measured glycocalyx injury and endothelial activation biomarkers within 48 hours of hospital admission. The primary outcome was the risk of mortality from all causes and the secondary outcomes were the risk of developing respiratory failure (RF) and multiple organ dysfunction syndrome (MODS) in patients with elevations of these biomarkers. A total of 17 studies (3,529 patients) were included: 11 evaluated syndecan-1 (n=2,397) and 6 endocan (n=1,132). Syndecan-1 was higher in the group of patients who died than in those who survived [255 ng/mL (IQR: 139-305) vs. 83 ng/mL (IQR:40-111); p=0.014]. Patients with elevated syndecan-1 had a greater risk of death (OR 2.32; 95% CI 1.89, 3.10: p<0.001), MODS (OR 3.3; 95% CI 1.51, 7.25: p=0.003;), or RF (OR 7.53; 95% CI 1.86-30.45: p=0.005). Endocan was higher in patients who died [3.1 ng/mL (IQR 2.3, 3.7) vs. 1.62 ng/mL (IQR 1.2, 5.7); OR 9.53; 95% CI 3.34, 27.3; p<0.001], who had MODS (OR 8.33; 95% CI 2.07, 33.58; p=0.003) and who had RF (OR 9.66; 95% CI 2.26, 43.95; p=0.002). Patients with sepsis and abnormal glycocalyx injury and endothelial activation biomarkers have a greater risk of developing respiratory failure, multiple organ failure, and death. Microcirculatory impairment should be routinely evaluated in patients with sepsis, using biomarkers to stratify risk groups.

Endothelial glycocalyx degradation in multisystem inflammatory syndrome in children related to COVID-19

Multisystem inflammatory syndrome in children (MIS-C) represents a rare but severe complication of severe acute respiratory syndrome coronavirus 2 infection affecting children that can lead to myocardial injury and shock. Vascular endothelial dysfunction has been suggested to be a common complicating factor in patients with coronavirus disease 2019 (COVID-19). This study aims to characterize endothelial glycocalyx degradation in children admitted with MIS-C. We collected blood and urine samples and measured proinflammatory cytokines, myocardial injury markers, and endothelial glycocalyx markers in 17 children admitted with MIS-C, ten of which presented with inflammatory shock requiring intensive care admission and hemodynamic support with vasopressors. All MIS-C patients presented signs of glycocalyx deterioration with elevated levels of syndecan-1 in blood and both heparan sulfate and chondroitin sulfate in the urine. The degree of glycocalyx shedding correlated with tumor necrosis factor-α concentration. Five healthy age-matched children served as controls. Patients with MIS-C presented severe alteration of the endothelial glycocalyx that was associated with disease severity. Future studies should clarify if glycocalyx biomarkers could effectively be predictive indicators for the development of complications in adult patients with severe COVID-19 and children with MIS-C.Key messagesChildren admitted with MIS-C presented signs of endothelial glycocalyx injury with elevated syndecan-1 and heparan sulfate level.Syndecan-1 levels were associated with MIS-C severity and correlated TNF-α concentration.Syndecan-1 and heparan sulfate may represent potential biomarkers for patients with severe COVID-19 or MIS-C.

Association Between Syndecan-1, Fluid Overload, and Progressive Acute Kidney Injury After Adult Cardiac Surgery

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery and the prognosis of AKI worsens with the increase in AKI severity. Syndecan-1(SDC-1) is a biomarker of endothelial glycocalyx degradation. Fluid overload (FO) is associated with poor outcomes in AKI patients and may be related to the damage of endothelial function. This study aimed at demonstrating the association between elevated SDC-1, FO, and AKI progression.Methods: In this prospective study, we screened patients who underwent cardiac surgery and enrolled patients who experienced an AKI within 48 h after surgery from December 1, 2018 to January 31, 2019. Blood and urine samples were collected at the time of AKI diagnosis for plasma SDC-1 (pSDC-1) and urine SDC-1 (uSDC-1) measurements. Fluid balance (FB) = accumulated [fluid intake (L) - fluid output (L)]/body weight (kg) × 100%. FO was defined as FB > 5%. The primary endpoint was progressive AKI, defined as AKI progression from a lower to a higher stage. The patients were divided into progressive AKI group vs. non-progressive AKI group.Results: The quartiles of pSDC-1 concentration (117.3 [67.4, 242.3] ng/mL) showed a graded association with the incidence of progressive AKI, ranging from 5.0, 11.9, 32.6 to 52.4% (p for trend < 0.001). Multivariate logistic regression showed that increased pSDC-1 was an independent risk factor for progressive AKI. The AUC-ROC area of pSDC-1 concentration in predicting AKI progression was 0.847. Linear regression showed a positive correlation between FB and pSDC-1 concentration (R2 = 0.384, p < 0.001). In patients with FO, the progressive AKI incidence was significantly higher in the high pSDC-1 (≥117.3 ng/mL) subgroup than in the low pSDC-1 subgroup (58.3 vs. 17.6%, OR = 9.167, P = 0.005). In patients without FO, the progressive AKI incidence was also significantly higher in the high pSDC-1 subgroup with a lower odds ratio (30.4 vs. 7.4%, OR = 6.714, P = 0.002).Conclusion: Elevated pSDC-1 concentration was associated with progressive AKI after cardiac surgery and showed good predictive ability for progressive AKI. FB was related to the increase of pSDC-1. The interaction between pSDC-1 and FB may further aggravate the progression of AKI.

Elevated Syndecan-1 after Trauma and Risk of Sepsis: A Secondary Analysis of Patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial

Endotheliopathy of trauma is characterized by breakdown of the endothelial glycocalyx. Elevated biomarkers of endotheliopathy, such as serum syndecan-1 (Synd-1) ≥ 40 ng/mL, have been associated with increased need for transfusions, complications, and mortality. We hypothesized that severely injured trauma patients who exhibit elevated Synd-1 levels shortly after admission have an increased likelihood of developing sepsis. We analyzed a subset of patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who survived at least 72 hours after hospital admission, and we determined elevated Synd-1 levels (≥ 40 ng/mL) 4 hours after hospital arrival. Sepsis was defined a priori as meeting systemic inflammatory response criteria and having a known or suspected infection. Univariate analysis was performed to identify variables associated with elevated Synd-1 levels and sepsis. Significant variables at a value of p < 0.2 in the univariate analysis were chosen by purposeful selection and analyzed in a mixed effects multivariate logistic regression model to account for the 12 different study sites. We included 512 patients. Of these, 402 (79%) had elevated Synd-1 levels, and 180 (35%) developed sepsis. Median Synd-1 levels at 4 hours after admission were 70 ng/dL (interquartile range [IQR] 36 to 157 ng/dL) in patients who did not develop sepsis, and 165ng/dL [IQR 67 to 336 ng/dL] in those who did (p < 0.001). Adjusting for treatment arm and site, multivariable analyses revealed that elevated Synd-1 status, Injury Severity Score (ISS), and total blood transfused were significantly associated with an increased likelihood of developing sepsis. Elevated Synd-1 levels 4 hours after admission in severely injured adult trauma patients who survived the initial 72 hours after hospital admission are associated with subsequent sepsis.

Acute Traumatic Endotheliopathy in Isolated Severe Brain Injury and Its Impact on Clinical Outcome.

Study design: Prospective observational cohort. Objective: To investigate the difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic brain injury (TBI) patients with/without early coagulopathy. A secondary objective was to compare the effects of the degree of TBI endotheliopathy on hospital mortality among patients with TBI-associated coagulopathy (TBI-AC). Methods: Data was prospectively collected on isolated severe TBI (sTBI) patients with Glasgow Coma Scale (GCS) ≤8 less than 12 h after injury admitted to a level I trauma centre. Isolated sTBI patients with samples withdrawn prior to blood transfusion were stratified by conventional coagulation tests as coagulopathic (prothrombin time (PT) ≥ 16.7 s, international normalized ratio (INR) ≥ 1.27, and activated partial thromboplastin time (aPTT) ≥ 28.8 s) and non-coagulopathic. Twenty healthy controls were also included. Plasma levels of thrombomodulin and syndecan-1 were estimated by ELISA. With receiver operating characteristic curve (ROC) analysis, we defined endotheliopathy as a syndecan-1 cut-off level that maximized the sum of sensitivity and specificity for predicting TBI-AC. Results: Inclusion criteria were met in 120 cases, with subjects aged 35.5 ± 12.6 years (88.3% males). TBI-AC was identified in 50 (41.6%) patients, independent of age, gender, and GCS, but there was an association with acidosis (60%; p = 0.01). Following isolated sTBI, we found insignificant changes in soluble thrombomodulin (sTM) levels between patients with isolated TBI and controls, and sTM levels were lower in coagulopathic compared to non-coagulopathic patients. Elevations in plasma syndecan-1 (ng/mL) levels were seen compared to control (31.1(21.5–30.6) vs. 24.8(18.5–30.6); p = 0.08). Syndecan-1(ng/mL) levels were significantly elevated in coagulopathic compared to non-coagulopathic patients (33.7(21.6–109.5) vs. 29.9(19.239.5); p = 0.03). Using ROC analysis (area under the curve = 0.61; 95% Confidence Interval (CI) 0.50 to 0.72), we established a plasma syndecan-1 level cutoff of ≥30.5 ng/mL (sensitivity % = 55.3, specificity % = 52.3), with a significant association with TBI-associated coagulopathy. Conclusion: Subsequent to brain injury, elevated syndecan-1 shedding and endotheliopathy may be associated with early coagulation abnormalities. A syndecan-1 level ≥30.5 ng/mL identified patients with TBI-AC, and may be of importance in guiding management and clinical decision-making.

Alterations of Endothelial Glycocalyx During Orthotopic Liver Transplantation in Patients With End-Stage Liver Disease.

Endothelial glycocalyx participates in the maintenance of vascular integrity, and its perturbations cause capillary leakage, loss of vascular responsiveness, and enhanced adhesion of leukocytes and platelets. We hypothesized that marked shedding of the glycocalyx core protein, syndecan-1, occurs in end-stage liver disease (ESLD) and that it increases during orthotopic liver transplantation (OLT). We further evaluated the effects of general anesthesia on glycocalyx shedding and its association with acute kidney injury (AKI) after OLT. Thirty consecutive liver transplant recipients were enrolled in this prospective study. Ten healthy volunteers served as a control. Acute kidney injury was defined by Acute Kidney Injury Network criteria. Plasma syndecan-1 was significantly higher in ESLD patients than in healthy volunteers (74.3 ± 59.9 vs 10.7 ± 9.4 ng/mL), and it further increased significantly after reperfusion (74.3 ± 59.9 vs 312.6 ± 114.8 ng/mL). The type of general anesthesia had no significant effect on syndecan-1. Syndecan-1 was significantly higher during the entire study in patients with posttransplant AKI stage 2 or 3 compared to patients with AKI stage 0 or 1. The area under the curve of the receiver operating characteristics curve of syndecane-1 to predict AKI stage 2 or 3 within 48 hours after reperfusion was 0.76 (95% confidence interval, 0.57-0.89, P = 0.005). Patients with ESLD suffer from glycocalyx alterations, and ischemia-reperfusion injury during OLT further exacerbates its damage. Despite a higher incidence of AKI in patients with elevated syndecan-1, it is not helpful to predict de novo AKI. Volatile anesthetics did not attenuate glycocalyx shedding in human OLT.

Serum syndecan-1, basic fibroblast growth factor and osteoprotegerin in myeloma patients at diagnosis and during the course of the disease.

Neovascularisation and bone resorption are related to myeloma disease activity. To investigate the possible prognostic importance of serum syndecan-1, basic fibroblast growth factor (bFGF) and osteoprotegerin (OPG) levels, the relationship between them, with parameters of disease activity and the effect of treatment on their levels. Twenty-seven patients were studied from diagnosis and an additional five from remission, for a median follow-up of 40 months. Twenty-three patients received chemotherapy plus bisphosphonates and nine only bisphosphonates. Sera from 11 healthy individuals (HI) were used as controls. Cytokines were determined by commercially available enzyme-linked immunosorbent assays (ELISA) kits. In HI, median syndecan-1 was 40 ng/mL (28-75), bFGF 8 pg/mL (7-30), OPG 35 pg/mL (4-100). Pretreatment median serum syndecan-1 was 177.5 ng/mL (34-3500), bFGF 11.5 pg/mL (8-65) and OPG 100 pg/mL (4-1000). Pretreatment syndecan-1, bFGF and OPG serum levels were increased in patients compared with HI (P = 0.001, 0.03 and 0.01, respectively). Syndecan-1 and bFGF levels were correlated with stage (P = 0.004 and 0.03, respectively). Both syndecan-1 and OPG levels were correlated with beta2M (P = 0.04 and 0.01, respectively). Patients with elevated syndecan-1 and bFGF serum levels had shorter survival than patients with normal levels (P = 0.01 and 0.05, respectively). After chemotherapy syndecan-1 and OPG levels were found to be decreased in responders and syndecan-1 level was reduced in patients receiving bisphosphonates alone. Pretreatment syndecan-1, bFGF and OPG levels were found to be increased at diagnosis. Syndecan-1 and OPG fluctuated according to MM activity. Elevated serum syndecan-1 and bFGF levels predicted short survival.

Elevated levels of shed syndecan‐1 correlate with tumour mass and decreased matrix metalloproteinase‐9 activity in the serum of patients with multiple myeloma

Sera from 20 myeloma patients and 12 normal controls were analysed for the presence of syndecan-1 and matrix metalloproteinase-9 (MMP-9). The level of syndecan-1 in the serum was elevated in 7/20 (3 5%) myeloma patients whilst 6/19 patients (31%) had decreased serum MMP-9 activity. The presence of increased syndecan-1 was associated with decreased serum MMP-9. Both elevated syndecan-1 and decreased MMP-9 were associated with higher marrow plasmacytosis, serum beta-2 microglobulin and paraprotein levels. These data provide evidence that the syndecan-1 ectodomain is shed in vivo. Quantitation of serum syndecan-1 may be a useful measure of tumour mass and may have important implications for myeloma biology.