Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis

Giubilei, Franco; Antonini, Giovanni; Legge, Silvia Di; Sormani, MP; Pantano, P.; Antonini, R; Sepe‐Monti, Micaela; Caramia, Francesca; Pozzilli, Carlo

doi:10.1034/j.1600-0404.2002.01334.x

Cited by 72 publications

(72 citation statements)

References 13 publications

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“…This hypothesis is supported by data suggesting that MS patients who produce anti-IFNbeta binding antibodies have an increased incidence of autoreactive antibodies, including antiphospholipid and antithyroid antibodies [20]. The possible involvement of lipoprotein metabolism in NAbs production is of further interest in the context of other studies [7,8], implicating a disturbance of this metabolism in MS and the potential benefit of statin monotherapy in these patients [21].…”

Section: Discussionsupporting

confidence: 63%

“…However, metabolic characteristics also influence immune responses, and hence might affect NAbs development in MS patients. For example, recent data have emphasized the relationships between lipoprotein metabolism and both innate and adaptive immunity [5,6]; alterations in plasma lipoproteins levels have also been found in MS patients [7,8]. However, the pathogenic and clinical importance of these alterations in MS remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

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Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

et al. 2010

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Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a onestandard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

et al. 2010

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“…Giubilei et al, in 2002, studied plasma lipoproteins and magnetic resonance imaging (MRI) in patients with a first clinical episode suggestive of MS (CIS), supporting the findings in EAE [13]. These authors observed high total and HDL-cholesterol in these patients and a significant correlation between disease activity (as assessed by MRI) and both total and LDL-cholesterol levels.…”

Section: Multiple Sclerosissupporting

confidence: 59%

“…HDL effects include an inhibition of cytocine-induced expression of adhesion molecules in endothelial cells, which could further depress brain parenchyma immune reactivity [46]. As mentioned, higher levels of plasma HDL were found in CIS and RR-MS and were associated with a lower probability in development of acute inflammatory lesions in these patients [13,[16][17]. Recently, preliminary evidence from our group suggests that higher plasma HDL levels are associated with an increased intrathecal IgG synthesis in these patients [47].…”

Section: Pathophysiological Mechanismsmentioning

confidence: 99%

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

Sena¹,

Capela²,

Nóbrega³

et al. 2012

Lipoproteins - Role in Health and Diseases

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“…In this research, we leverage a range of CSF measures to understand the contributions of lipid profi le variables to pathophysiological increases in BBB permeability and to immune activity in CSF. We focused on serum cholesterol profi les because there is an emerging body of data suggesting associations between serum cholesterol profi les and MRI measures of lesional and neurodegenerative injury in MS patients (8)(9)(10)(11)(12)(13). In our previous work, we found an adverse association between greater serum cholesterol and MS disease progression.…”

Section: Csf Assaysmentioning

confidence: 94%

Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients

Fellows

Uher

Browne

et al. 2015

Journal of Lipid Research

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Blood-brain barrier (BBB) injury creates a permissive environment for infl ammation and the extravasation of immune cells ( 1 ) in multiple sclerosis (MS), a chronic infl ammatory and neurodegenerative disease of the CNS ( 2 ). Compromised BBB structural integrity is necessary for the formation of contrast-enhancing lesions (CELs), which are frequently found on brain MRI from MS patients, even in the absence of clinical relapses. CELs represent focal areas with compromised BBB structural integrity and are associated with parenchymal and meningeal infl ammation ( 3 ). Increased BBB water permeability precedes the appearance of CELs and is pervasive in normal-appearing white matter ( 4 ).In CNS regions with loss of BBB structural integrity, there is increased permeability to macromolecules such as proteins, albumin, and immunoglobulins, that are normally Abstract The purpose of this work was to investigate the associations of serum cholesterol and apolipoproteins with measures of blood-brain barrier (BBB) permeability and CNS infl ammation following the fi rst clinical demyelinating event. This study included 154 patients [67% female; age, 29.5 ± 8.2 years (mean ± SD)] enrolled in a multi-center study of interferon ␤ 1-a treatment following the fi rst demyelinating event. Blood and cerebrospinal fl uid (CSF) were obtained at screening prior to treatment. A comprehensive serum lipid profi le and multiple surrogate markers of BBB breakdown and CNS immune activity were obtained. Higher levels of serum HDL cholesterol (HDL-C) and ApoA-I were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgG level (all P Յ 0.001 for HDL-C and all P < 0.01 for ApoA-I). HDL-C was also associated with CSF CD80+ ( P < 0.001) and with CSF CD80+CD19+ ( P = 0.007) cell frequencies. Higher serum HDL is associated

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Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis

Cited by 72 publications

References 13 publications

Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients

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