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1.
J Neuroimmunol ; 148(1-2): 206-11, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14975603

ABSTRACT

It has recently become clear that interferon-beta (IFN-beta) treatment is effective in ameliorating relapsing-remitting multiple sclerosis (RRMS) through an as yet unidentified mechanism. As there is no recognisable biological indicator to predict responsiveness to IFN-beta treatment, we have investigated fluctuations in serum sHLA-I levels in MS patients undergoing IFN-beta 1b therapy. Serum sHLA-I concentrations measured by enzyme-linked immunosorbent assay (ELISA) were assessed at baseline and, longitudinally, over a period of 18 months after the start of treatment in 29 RRMS patients grouped as responders and nonresponders according to their clinical response to IFN-beta 1b therapy. Thirty-nine healthy volunteers served as controls. Serum sHLA-I concentrations were significantly higher (p<0.001) in pretreated RRMS patients than in healthy donors. In MS patients, changes in mean serum levels of sHLA-I from baseline showed a temporal pattern characterized by a strong increase in the first trimester of treatment, a return toward basal values in the following 6 months, a slight decline at 12th and 15th months and a further moderate increase at the 18th month. Mean serum sHLA-I levels were significantly more elevated in responders than in nonresponders at the first (p<0.02), second (p<0.01), and at third (p<0.02) months after the beginning of treatment and significantly lower (p<0.01) at the time of relapses in comparison to baseline values. Overall, these results seem to indicate that IFN-beta 1b can modulate fluctuations in serum sHLA-I levels and argue in favour of a potential role for serum levels of sHLA-I as a sensitive marker to monitor response to IFN-beta treatment in MS.


Subject(s)
HLA Antigens/blood , Interferon-beta/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Antineoplastic Agents/therapeutic use , Disability Evaluation , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Interferon beta-1b , Longitudinal Studies , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/blood , Statistics, Nonparametric , Time Factors
2.
J Neuroimmunol ; 142(1-2): 149-58, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14512174

ABSTRACT

We have investigated the presence of non-classical soluble HLA-G molecules (sHLA-G) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients and the possible relationships between CSF levels of sHLA-G, classical soluble HLA-I (sHLA-I) molecules, IL-10 amounts and Magnetic Resonance Imaging (MRI) findings were evaluated. We studied by ELISA technique the sHLA-I, sHLA-G and IL-10 levels in CSF of 50 relapsing-remitting (RR) MS patients stratified according to clinical and MRI evidence of disease activity. Thirty-six patients with other inflammatory neurological disorders (OIND) and 41 with non-inflammatory neurological disorders (NIND) were used as controls. CSF mean levels were significantly higher in MS and OIND than in NIND for sHLA-I (p<0.001) and in MS than in controls for sHLA-G (p<0.001), with no differences among the various groups for IL-10 mean concentrations. An increase in CSF sHLA-I was found in MS patients with Gd-enhancing lesions (p<0.01), while sHLA-G and IL-10 were more represented in MS patients without lesional activity on MRI scans (p<0.02). In MRI-inactive MS, CSF IL-10 mean concentrations were significantly greater in patients with CSF-detectable levels of sHLA-G than in those without any evidence of CSF sHLA-G expression (p<0.05). Our findings suggest that CSF classical sHLA-I and non-classical sHLA-G levels may modulate MS activity as assessed by MRI acting in opposite directions. The association observed between sHLA-G and IL-10 when Gd-enhancing lesion resolved indicates a potential immunoregulatory role for IL-10 in the control of MS disease activity by shifting the sHLA-I/sHLA-G balance towards sHLA-G response.


Subject(s)
HLA Antigens/cerebrospinal fluid , Histocompatibility Antigens Class I/cerebrospinal fluid , Interleukin-10/cerebrospinal fluid , Magnetic Resonance Imaging , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Multiple Sclerosis, Relapsing-Remitting/immunology , Adult , Antibodies, Monoclonal , Blotting, Western , Enzyme-Linked Immunosorbent Assay/statistics & numerical data , Female , Gadolinium , HLA Antigens/immunology , HLA-G Antigens , Histocompatibility Antigens Class I/immunology , Humans , Inflammation/cerebrospinal fluid , Inflammation/diagnosis , Inflammation/immunology , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/statistics & numerical data , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Nervous System Diseases/cerebrospinal fluid , Nervous System Diseases/diagnosis , Nervous System Diseases/immunology , Solubility
3.
J Neuroimmunol ; 133(1-2): 151-9, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12446018

ABSTRACT

The goal of our study was to clarify the contribution of soluble human leukocyte antigens class I (sHLA-I) in multiple sclerosis (MS) immune dysregulation. We retrospectively evaluated by ELISA cerebrospinal fluid (CSF) and serum sHLA-I levels in 79 relapsing-remitting (RR), 26 secondary progressive (SP) and 15 primary progressive (PP) MS patients stratified according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. One hundred and nine patients with other inflammatory neurological disorders (OIND), 88 with noninflammatory neurological disorders (NIND) and 82 healthy donors were used as controls. An intrathecal synthesis of sHLA-I detected by a specific index was significantly more consistent in MS than in controls, with more pronounced values in MS patients with relapses and MRI enhancing brain lesions. A decrease in serum sHLA-I concentrations was observed in MS patients with demyelinating attacks, while an increase in CSF levels of sHLA-I was found in MS patients with lesional activity on MRI scans. This association between intrathecal synthesis and reciprocal fluctuations of CSF and serum levels of sHLA-I in clinically and MRI active MS seems to suggest a potential role for CSF and serum levels of sHLA-I as a sensitive marker of immune activation taking place both intrathecally and systemically in MS.


Subject(s)
Central Nervous System/immunology , Histocompatibility Antigens Class I/blood , Histocompatibility Antigens Class I/cerebrospinal fluid , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Adult , Central Nervous System/metabolism , Central Nervous System/pathology , Disease Progression , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/pathology , Predictive Value of Tests , Retrospective Studies
4.
Neuroepidemiology ; 21(5): 251-4, 2002.
Article in English | MEDLINE | ID: mdl-12207154

ABSTRACT

OBJECTIVES: The etiology of epilepsy remains unknown in most cases. We sought to investigate the role of some pre-, peri- and postnatal factors in the etiology of idiopathic and cryptogenetic partial epilepsy. METHODS: We carried out a community-based case-control study using the incidence cohort of epileptic patients living in the district of Copparo, in the province of Ferrara, Italy. The study was performed in 55 cases and 165 controls. A standardized questionnaire was used to collect information in face-to-face interviews. RESULTS: Multivariate logistic regression analysis found that a personal history of febrile convulsions [odds ratio (OR) = 4.01, 95% confidence interval (CI) = 1.3-19.1] and a family history of seizures in first-degree relatives (OR = 4.5, 95% CI = 1.8-18.6) were independent risk factors for the condition under study. We failed to demonstrate an association between partial epilepsy and previously suggested perinatal risk factors. CONCLUSION: The findings of this study further support the hypothesis of a genetic propensity for seizures, which may be expressed early by the occurrence of febrile convulsions.


Subject(s)
Epilepsies, Partial/etiology , Epilepsies, Partial/genetics , Genetic Predisposition to Disease , Prenatal Exposure Delayed Effects , Adolescent , Adult , Case-Control Studies , Child , Epilepsies, Partial/epidemiology , Female , Humans , Male , Pedigree , Pregnancy , Regression Analysis , Risk Factors , Seizures, Febrile/complications
5.
Arch Neurol ; 59(1): 48-53, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11790230

ABSTRACT

BACKGROUND: Studies have reported circadian variation in the onset of ischemic stroke, which may carry important pathophysiological implications. However, there is no detailed information about circadian variations among the subtypes of stroke. OBJECTIVE: To determine whether subgroups of patients with ischemic stroke with specific clinical characteristics would exhibit different circadian patterns, to more systematically examine the role of possible triggering or precipitating factors. DESIGN AND SETTING: Analysis of the effects of demographic, medical, and pathophysiological factors on the circadian pattern of an unselected series of patients with ischemic stroke consecutively admitted to our hospital. RESULTS: The study included 1656 patients. As in other studies, the peak of stroke onset occurred in the morning, with a second peak in the evening. Circadian variation in ischemic stroke onset was shown to be independent of clinical variables considered. CONCLUSIONS: Our study confirms the circadian rhythm of stroke reported in previous studies. There is a chronological pattern of ischemic stroke in the morning, which appears to be independent of the presence of risk factors and of clinical stroke subtypes. The role of circadian variability of blood pressure (present in patients with and without hypertension) and a concurrent morning hypercoagulability are suggested as possible determinants of this pattern. Preventive pharmacological interventions aimed at specifically targeting the morning rise in risk factors could be advantageous in reducing the overall risk of ischemic stroke.


Subject(s)
Brain Ischemia/epidemiology , Circadian Rhythm , Stroke/epidemiology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Risk Factors , Sleep
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