[Concentration of soluble forms of selectins in serum and in cerebrospinal fluid in group of patients with neuroborreliosis--a preliminary study]. / Stezenie rozpuszczalnych form selektyn w surowicy i plynie mózgowo-rdzeniowym u chorych na neuroborelioze--badania wstepne.

UNLABELLED: The results of the research already done, suggest an important role of selectins in inflammatory process of various etiology. Lack of selectins or their ligands causes severe complications, such as chronic inflammatory processes. The aim of this study was to analyze the role of selectins sL, sE and sP in the development and course of neuroborreliosis in the form of meningitis. We have also analyzed the influence of treatment on changes of selectins' concentration in serum and cerebrospinal fluid. MATERIAL AND METHODS: We have analyzed 17 patients with neuroborreliosis presenting as meningitis, in whom we measured by immunoenzymatic method concentration of selectins sL, sP and sE in blood and cerebrospinal fluid before and after 4-week therapy with cefotaxim. We used Human sL-selectin, Human sE-selectin and Human sP-selectin kits produced by Bender Med. Systems, Austria. Control group for measurement of concentration of selectins in serum consisted of 8 healthy patients. Control group for measurement of concentration of selectins in cerebrospinal fluid consisted of 8 patients, in whom lumbar puncture excluded inflammatory disease of the central nervous system. RESULTS: In serum concentration of selectins sL and sP was significantly higher comparing to control group. After treatment concentration of these selectins decreased, but still was significantly higher than in control group. Only concentration of selectin sE was significantly lower than in control group and after treatment decreased further remaining lower comparing to control group. In cerebrospinal fluid concentration of selectin sL was significantly higher comparing to control group and increased after treatment. Concentration of selectins sE and sP increased before treatment and decreased after treatment, but still remained elevated comparing to control group. CONCLUSIONS: Persistence of increased concentration of selectins sP and sL in serum and also of selectin sE in cerebrospinal fluid in patients with neuroborreliosis after completed antibiotic therapy and regression of clinical symptoms can suggest permanence of chronic inflammatory state in consequence of survival of B. burgdorferi spirochetes in affected tissues.

Increase in adhesion molecules in cerebrospinal fluid of children with mumps and mumps meningitis.

Adhesion molecules play a key role in leucocyte migration into the central nervous system (CNS). Concentrations of endothelial-derived soluble intercellular adhesion molecule-1 (sICAM-1) and leucocyte-originated soluble L-selectin (sL-selectin) in cerebrospinal fluid (CSF) of children with mumps meningitis (mononuclear pleocytosis, n = 33) and mumps (absence of pleocytosis, n = 9) were compared with values from age-matched control group (n = 19). In 14 patients from the meningitis group, adhesion molecule levels together with albumin concentration were estimated in paired CSF/serum samples to calculate concentration quotients and determine molecule intrathecal release. Both sICAM-1 (median 3.44 versus 0.86 ng/ml; P < 0.0001) and sL-selectin (median 29.91 versus 8.52 ng/ml; P < 0.0001) concentrations in CSF were increased in mumps meningitis patients compared with controls. Increased levels of the selected adhesion molecules were also observed in mumps patients without CNS involvement when compared with controls (median sICAM-1: 1.14 versus 0.86 ng/ml, sL-selectin: 13.54 versus 8.52 ng/ml; P < 0.01). Additionally, the concentration of adhesion molecules was found to correlate with CSF leucocyte count. Considerable correlation of sICAM-1 and sL-selectin quotients and corresponding albumin quotients suggests that a majority of the soluble adhesion molecules originated from the bloodstream. Analysis of adhesion molecule levels demonstrated indirect evidence of brain-derived fractions. Our results suggest the involvement of adhesion molecules during the early phase of mumps meningitis.

[Clinical significance of the detection of the sL-selectin level in patients with acute leukemia].

OBJECTIVE: To study the relationship between the episode and state of acute leukemia and the level of soluble L-selectin (sL-selectin) in the plasma and cerebrospinal fluid. METHODS: With a sandwich enzyme-linked immunosorbent assay (ELISA), the levels of sL-selectin in the plasma of 40 patients with acute leukemia and in the cerebrospinal fluid of 28 patients with acute lymphoblastic leukemia were measured, and compared with 20 controls. RESULTS: The levels of sL-selectin were significantly higher in the patients with untreated and therapy-resistant acute leukemia or leukemia relapse than those in the complete remission patients and the controls (P < 0.001). The levels of SL-selectin were related to the clinical course of acute leukemia. CONCLUSION: Monitoring the sL-selectin level may be useful for evaluating leukemia activity, in particular for the detection of leukemia relapse and meningeal infiltration.

Concentration of soluble adhesion molecules (sVCAM-1, sICAM-1 and sL-selectin) in the cerebrospinal fluid and serum of patients with multiple sclerosis and systemic lupus erythematosus with central nervous involvement.

OBJECTIVES: The aim of the present study was to investigate the role of soluble adhesion molecules in the pathogenesis of multiple sclerosis (MS) and systemic lupus erythematosus (SLE) with demyelinating syndrome. METHODS: Paired cerebrospinal fluid (CSF) and serum samples were analysed by an ELISA method to determine the concentrations of sVCAM-1, sICAM-1 and sL-selectin. Intrathecal syntheses of the adhesion molecules were calculated. RESULTS: Elevated serum and CSF concentrations of sVCAM-1 were present in all patient groups. Intrathecal synthesis of sVCAM-1 was present in the relapsing-remitting and secondary progressive forms of MS. Intrathecal synthesis of sICAM-1 was observed in all clinical forms of MS. MS patients with progressive forms of the disease and SLE patients were characterised by intrathecal synthesis of sL-selectin. CONCLUSIONS: The data presented suggest that (1) blood-brain barrier damage can be assumed both in systemic disease and organ-specific disease (sVCAM-1), (2) clinical forms of MS differ from each other in respect to concentrations of adhesion molecules and (3) similar immunological events in the central nervous system of SLE patients with demyelinating syndrome and progressive forms of MS can be assumed (sL-selectin).

Soluble L-selectin levels in serum and cerebrospinal fluid in patients with multiple sclerosis and systemic lupus erythematosus.

Soluble L-selectin (sL-selectin) concentrations were measured in paired samples of serum and cerebrospinal fluid by an ELISA method. Patients with several forms of multiple sclerosis (MS) and systemic lupus erythematosus with central nervous system involvement (SLE-CNS) were investigated. Elevated CSF sL-selectin concentrations were found in patients with SLE-CNS (7.62 +/- 3.31 ng/ml) and with relapsing-remitting form of MS (6.99 +/- 4.72 ng/ml) compared to the control group (4.00 +/- 0.95 ng/ml). The data presented suggest some similarities between inflammatory/immunological events in the central nervous system in patients with SLE-CNS and relapsing-remitting form of MS. Immunological heterogeneity in MS is suspected.

Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage.

OBJECT: The goal of this study was to explore whether the levels of soluble adhesion molecules were elevated in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). This association was suggested by the known inflammatory response in vasospasm and the role of vascular adhesion molecules in regulating leukocytic adhesion to, and migration across, vascular endothelium. METHODS: A prospective analysis was performed on CSF samples obtained in 17 patients who had suffered a recent aneurysmal SAH and in 16 control patients by using quantitative enzyme-linked immunosorbent assays for E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and L-selectin. Levels of soluble forms of E-selectin (p=0.0013), ICAM-1 (p=0.0001), and VCAM-1 (p=0.048) were found to be elevated in the CSF of patients after SAH compared with levels in the CSF of norminal controls, patients with unruptured aneurysms, and patients tested months after SAH occurred. In addition, individual patients tested at the time of their initial ictus demonstrated a fall in adhesion molecule levels over time. Levels of E-selectin (p=0.044) were highest in patients who later developed moderate or severe vasospasm. CONCLUSIONS: Adhesion molecules are known to be involved in white cell adherence to the endothelium and subsequent diapedesis and migration in which a role in initiation of tissue damage is postulated. The authors have demonstrated the elevation of three adhesion molecules, with severely elevated levels of E-selectin seen in patients who later develop vasospasm. A correlation with a role of vascular adhesion molecules in the pathogenesis of cerebral vasospasm is suggested.

Raised CSF levels of soluble adhesion molecules across the clinical spectrum of multiple sclerosis.

Endothelial activation is considered an important step in multiple sclerosis (MS) lesion formation, elevated cerebrospinal fluid (CSF) and serum levels of certain adhesion molecules being associated with varying stages of disease activity and clinical course. CSF and serum sVCAM-1, sICAM-1, sE-selectin and sL-selectin were measured by ELISA in 16 primary progressive (PPMS), 16 secondary progressive (SPMS) and 43 relapsing-remitting MS patients (RRMS) and compared with 20 inflammatory (IND) and 46 non-inflammatory neurological disease (NIND) controls. CSF sVCAM-1 and sICAM-1 were increased in all MS groups vs. NIND with no significant differences between the MS groups. CSF sE-selectin (p = 0.007) and the sE-selectin index (p = 0.01) were elevated in PPMS vs. RRMS in relapse, whilst serum sE-selectin was significantly raised in PPMS compared to RRMS in remission (p = 0.005), RRMS in relapse (p = 0.004), NIND (p = 0.03) and IND (p = 0.05). Adhesion molecule levels in both progressive MS groups were similar. These results provide evidence for a distinct inflammatory component in PPMS and for immunological heterogeneity between the clinical subgroups of MS.

Elevated serum levels of soluble E- and L-selectin in patients with human T-cell lymphotropic virus type I-associated myelopathy.

We compared soluble E-selectin (sE-selectin) and L-selectin (sL- selectin) levels in sera and cerebrospinal fluid (CSF) of 30 patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM), with those of 10 patients with the relapsing-remitting form of multiple sclerosis (MS), and 16 patients with other neurological diseases (OND). Serum levels of both sE-selectin and sL-selectin, as measured by enzyme-linked immunosorbent assay, were significantly elevated in patients with HAM, compared to patients with OND. In addition, serum levels of sL-selectin were significantly elevated in HAM patients compared to MS patients. No significant difference was found in CSF levels of sL-selectin between HAM patients and controls. However, HAM patients who had received blood transfusions had significantly higher CSF levels of sL-selectin than HAM patients without a past history of transfusions, suggesting that HAM patients with past history of transfusion have a more active immunological state in the central nervous system. sE-selectin was not detected in CSF of HAM patients and controls. This finding might be based on exaggerated inflammatory conditions following increased attachment of lymphocytes to activated endothelial cells in HAM patients.

Soluble L-selectin increases in the cerebrospinal fluid prior to meningeal involvement in children with acute lymphoblastic leukemia.

Soluble L-selectin was determined in the CSF samples of 20 children with CNS leukemia at the time they had blasts in CSF and/or clinical findings of CNS involvement; 17 CSF fluid samples were obtained from 17 of these 20 children, 29-91 days before the appearance of CSF cytological and/or clinical findings of CNS involvement; while 15 CSF samples were withdrawn from among the same group of children, after treatment of meningeal leukemia. In addition, CSF sL-selectin was also assayed in 17 children with ALL, who remained in complete remission at least for a year and, as controls, in 12 children without malignant or meningeal disorders. There was no significant difference in CSF sL-selectin levels between the children with ALL without evidence of meningeal involvement and the controls (1.34 +/- 0.21 ng/ml, 1.46 +/- 0.18 ng/ml respectively, p > 0.05). However, in children with CNS leukemia, not only at the time CNS involvement was diagnosed, but also 29-91 days before the diagnosis of CNS leukemia, the concentrations of the CSF sL-selectin (12.41 +/- 2.14 ng/ml, 7.70 +/- 1.60 ng/ml respectively) were significantly higher than those in controls (p < 0.001 and p < 0.01 respectively). After treatment and disappearance of the blasts in CSF, sL-selectin was found to be decreased and even normalized in the majority of children who had meningeal involvement (2.87 +/- 2.14 ng/ml). In 5 children, the CSF sL-selectin remained high, after the blasts in CSF had disappeared and CNS leukemia recurred within 3 months in 4 of these 5 children. In conclusion, assay of sL-selectin in CSF seems to be a good diagnostic tool in the detection of CNS involvement in children with ALL. This method may also be used as an indicator, in prediction of the CNS leukemia, which is going to develop.

Endothelial-derived adhesion molecules in bacterial meningitis: association to cytokine release and intrathecal leukocyte-recruitment.

The release of circulating isoforms of selectin- (L-selectin, ELAM-1) and immunoglobulin-type- (ICAM-1) adhesion molecules, responsible for accumulation of leukocytes at sites of tissue injury was studied in CSF and serum of 21 patients with bacterial meningitis and in healthy subjects. Their concentrations were compared with the intrathecal leukocyte recruitment and release of inflammatory cytokines. In contrast to serum concentrations of the leukocyte-derived adhesion molecule, sL-selectin, serum concentrations of endothelial-derived adhesion molecules, sELAM-1 and sICAM-1, were significantly increased in meningitis. No intrathecal synthesis of these adhesion molecules was observed. Serum levels of sELAM-1 were associated with extent of CSF pleocytosis and with concentrations of proinflammatory cytokines IL-1beta and TNF alpha in CSF, but not in serum. Therefore, expression of endothelial adhesion molecules i.e. ELAM-1 may be responsible for the massive intrathecal recruitment of potentially harmful leukocytes in patients with bacterial meningitis. Intrathecally released proinflammatory cytokines may represent the inducing signals for their endothelial upregulation.

Cerebrospinal fluid soluble L-selectin (sCD62L) in meningoencephalitis.

The leucocyte adhesion molecule L-selectin (CD62L) is rapidly cleaved off proteolytically after cell activation, generating soluble L-selectin (sCD62L) molecules. sCD62L concentrations were determined in 185 cerebrospinal fluid (CSF) samples obtained from children aged 1 month to 17 years. In 36 CSF samples of children with meningoencephalitis, sCD62L was significantly higher (median 209 fmol/ml) than in samples of children with other febrile diseases (n = 67, median 50 fmol/ml) or non-febrile disorders (n = 82, median 44 fmol/ml). There was a positive correlation between CSF protein and CSF sCD62L (rS = 0.68), suggesting that a disturbed blood-brain barrier contributes to raised sCD62L concentrations in the CSF. However, the CSF sCD62L/protein ratio of children with meningoencephalitis was significantly higher than in children with other febrile diseases or non-febrile disorders, indicating that sCD62L concentrations in children with meningoencephalitis were higher than expected from plasma leakage alone. It is concluded that both an impaired blood-brain barrier and the generation of sCD62L by infiltrating leucocytes contribute to raised CSF sCD62L concentrations in children with meningoencephalitis.

Circulating L-selectin in multiple sclerosis patients with active, gadolinium-enhancing brain plaques.

Leukocyte migration into inflammatory lesions is controlled by adhesion molecules. L-selectin is the adhesion molecule on leukocytes that is responsible for making the initial contact with endothelium. After establishing this contact, L-selectin is shed from the cell surface and present in the circulation as a functional soluble receptor. To investigate this initial adhesive event, we evaluated the presence of soluble L-selectin (sL-selectin) in serum and CSF of patients with multiple sclerosis (MS), viral encephalitis, and controls. MS patients with active, gadolinium-enhancing lesions on magnetic resonance imaging had significantly higher sL-selectin serum levels than controls (P < 0.05). These levels in MS patients correlated with the size of the enhancing lesions (P < 0.05), and with sL-selectin levels in CSF (P < 0.001). In viral encephalitis, in contrast, sL-selectin is elevated in CSF only (P < 0.001) and may derive from intrathecal leukocytes. These results show that the earliest adhesive events mediated by L-selectin indeed operate in active MS, and that sL-selectin will be of value in quantitating the extent of this inflammatory process.