Serum ferritin, transferrin and soluble transferrin receptor levels in                 multiple sclerosis patients

Over the last few years, increased evidence has supported the role of iron dysregulation in the pathogenesis of multiple sclerosis (MS), as iron is essential for myelin formation and oxidative phosphorylation. We studied indices of iron metabolism, such as serum iron, ferritin, transferrin and soluble transferrin receptor (sTFR) levels in 27 MS patients. Seven patients had chronic progressive active disease (CP-A), six had chronic progressive stable (CP-S), ten had relapsing—remitting active (RR-A) and four had relapsing—remitting stable (RR-S) disease. sTFR levels were found to be significantly higher in CP-A (P=0.021) and RR-A (P= 0.004) patients than in controls. sTFR levels were also elevated in CP-S patients but did not reach significance (P=0.064). sTFR values in RR-S patients were comparable to those found in controls (P=0.31). Ferritin levels were significantly elevated only in CP-A patients (P= 0.002). Patients of the CP group had significantly higher ferritin values than the RR patients (P= 0.004). Haemoglobin values as well as iron and transferrin levels were within normal limits in all patients. In conclusion, the increased serum sTFR and ferritin levels in nonanaemic MS patients with active disease reflect the increased iron turnover. The mild elevation of sTFR levels in CP-S patients may indicate active inflammation with ongoing oxidative damage that is not detectable by history or examination.

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Effectiveness and Safety of Long-Term Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients with Highly Active Disease

10.26226/morressier.59a3e8b6d462b8028d8953f4 ◽

2017 ◽

Author(s):

Galina Vorobeychik

Keyword(s):

Multiple Sclerosis ◽

Highly Active ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis ◽

Active Disease

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Venous Thrombosis in Multiple Sclerosis Patients after High-Dose Intravenous Methylprednisolone: The Preventive Effect of Enoxaparin

Thrombosis ◽

10.1155/2011/785459 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 9

Author(s):

Hossein Kalanie ◽

Ali Amini Harandi ◽

Shapoor Alidaei ◽

Daryoosh Heidari ◽

Saeed Shahbeigi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Venous Thrombosis ◽

High Dose ◽

Intravenous Methylprednisolone ◽

Relapsing Remitting ◽

Acute Attacks ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis ◽

Preventive Role

Aim. This study was designed to examine the possible role of high-dose intravenous methylprednisolone (IVMP) in the development of venous thrombosis (VT). The cerebral one anecdotally had been reported in patients with relapsing remitting multiple sclerosis (RRMS) in acute attacks and the possible preventive role of enoxaparin. Material and Methods. From a pool of 520 patients, 388 patients with definite RRMS who fulfilled entry characteristics were selected and randomly received either a 5-day course of daily 1 gr IVMP or the aforementioned plus 5 days of daily subcutaneous 40 units of enoxaparin according to a predefined protocol. Results. Mean age, gender ratio, mean relapse rate, and EDSS were similar in both groups of patients (P > 0.05). Finally, 366 patients remained in the study. Of 188 patients treated with IVMP with 855 relapses, 5 developed VT (0.37% per patient per year and 0.58% per each course of IVMP) within 3 to 15 days of starting therapy. None of the 178 patients who experienced 809 relapses who received IVMP plus enoxaparin developed such complications. Conclusion. The study implies that high-dose IVMP in MS exacerbation may increase the risk of VT and prophylactic anticoagulant treatment in this setting is warranted.

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NLRP3 polymorphisms and response to interferon-beta in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458517739137 ◽

2017 ◽

Vol 24 (11) ◽

pp. 1507-1510 ◽

Cited By ~ 4

Author(s):

Sunny Malhotra ◽

Melissa Sorosina ◽

Jordi Río ◽

Silvia Peroni ◽

Luciana Midaglia ◽

...

Keyword(s):

Multiple Sclerosis ◽

Interferon Beta ◽

Meta Analysis ◽

Nlrp3 Gene ◽

Radiological Criteria ◽

Pyrin Domain ◽

Relapsing Remitting ◽

Multiple Sclerosis Patients

We aimed to investigate whether NLR family, pyrin domain containing 3 (NLRP3) polymorphisms are associated with the response to interferon-beta (IFNβ) in multiple sclerosis (MS) patients. A total of 14 NLRP3 polymorphisms were genotyped in a cohort of 665 relapsing-remitting MS patients recruited across 5 centers and classified into responders and non-responders according to clinical-radiological criteria after 1 year of IFNβ treatment. A meta-analysis failed to demonstrate significant associations between the response to IFNβ and NLRP3 polymorphisms. These findings do not support a role of polymorphisms located in the NLRP3 gene and the response to IFNβ in MS patients.

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Profile of cytokine gene polymorphisms in Iranian multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458506070237 ◽

2007 ◽

Vol 13 (2) ◽

pp. 253-255 ◽

Cited By ~ 21

Author(s):

A Amirzargar ◽

F Khosravi ◽

S Dianat ◽

F Hushmand ◽

P Maryousef ◽

...

Keyword(s):

Multiple Sclerosis ◽

Gene Polymorphisms ◽

Cytokine Gene ◽

Immune Mediated ◽

Tnf Α ◽

Relapsing Remitting ◽

Cytokine Gene Polymorphisms ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

Background Cytokine gene polymorphisms have been extensively studied in association with different diseases. The role of cytokine gene polymorphisms in multiple sclerosis (MS), as a chronic immune-mediated neurodegenerative disease, has been previously reported. Materials and methods DNA samples were collected from 44 patients with relapsing-remitting multiple sclerosis (RRMS) and 140 unrelated healthy subjects. All participants in this study were matched for ethnicity. Cytokine gene SNPs were determined using the PCR-SSP method. Results and discussion We found no significant differences between MS patients and controls in most of the studied cytokine genes. Remarkable results were obtained for IL-2 GG —330 genotype (P = 0.06), IL-6 C —174 allele (P = 0.06), CG and GG genotypes (P < 0.001), and GG (P = 0.02) and CG (P < 0.001) haplotypes, and TNF-α A —238 allele (P < 0.001), GG (P = 0.003) and GA (P < 0.001) haplotypes. These results suggest that polymorphic variations of these pro-inflammatory cytokines play an important role in susceptibility to MS. Multiple Sclerosis 2007; 13: 253–255. http://msj.sagepub.com

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Massive Restrain of Cytotoxic B cells in the Peripheral Blood During Fingolimod and Natalizumab Treatments in Multiple Sclerosis Patients

10.21203/rs.3.rs-31940/v1 ◽

2020 ◽

Author(s):

Vinícius de Oliveira Boldrini ◽

Raphael Patrício da Silva Quintiliano ◽

Adriel dos Santos Moraes ◽

Carla Stella ◽

Ana Leda Figueiredo Longhini ◽

...

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

T Lymphocytes ◽

Peripheral Blood ◽

Antibody Therapy ◽

Healthy Donors ◽

Relapsing Remitting ◽

Anti Cd20 ◽

Multiple Sclerosis Patients

Abstract Background Recently, the success of anti-CD20 monoclonal antibody therapy brought a new light over the role of B cells in multiple sclerosis (MS) pathogenesis. Due to the expression pattern of CD20 during B cells ontogeny, this role seems to be extended beyond the antibodies' production and secretion. Therefore, here we investigated whether not only classical cytotoxic CD8+ T lymphocytes but also non-classical cytotoxic B cells may occur in the peripheral blood from relapsing-remitting MS (RRMS) patients. Methods 104 RRMS patients during different treatment and 58 healthy donors were studied. CD19, GzmB, Runx3 and CD49d expression was assessed by flow cytometry analyses. Results Patients treated with Natalizumab (NTZ) showed an increased percentage of CD8+GzmB+ when compared to other MS therapies, untreated RRMS patients and healthy volunteers. Similarly, and unexpected, massive cytotoxic behavior of B cells CD19+GzmB+ was observed in RRMS patients during Fingolimod (FTY) and NTZ therapies when compared to Glatiramer, Interferonβ, untreated MS patients and healthy donors. Conclusions During different MS treatments, B cells exhibit cytotoxic behavior resembling CD8+ T lymphocytes. This data suggest a possible involvement of “cytotoxic” B cells during MS pathology. Monitoring cytotoxic subsets might become an available marker for the risk of relapses and even for accessing therapeutic effectiveness in MS patients.

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The role of iron dysregulation in the pathogenesis of multiple sclerosis: an Egyptian study

Multiple Sclerosis Journal ◽

10.1177/1352458507085550 ◽

2008 ◽

Vol 14 (5) ◽

pp. 602-608 ◽

Cited By ~ 26

Author(s):

N Abo-Krysha ◽

L Rashed

Keyword(s):

Multiple Sclerosis ◽

Serum Level ◽

Iron Metabolism ◽

Transferrin Receptor ◽

Rating Scales ◽

Control Group ◽

Laboratory Assessment ◽

Secondary Progressive ◽

Normal Limits

Background Iron is essential for virtually all types of cells and organisms. The significance of iron for brain function is reflected by the presence of receptors for transferrin on brain capillary endothelial cells. Iron imbalance is associated with proinflammatory cytokines and oxidative stress, which have been implicated in the pathogenesis of multiple sclerosis (MS). Transferrin receptor (TfR) is the major mediator of iron uptake. Its expression is increased to facilitate iron entrance into the cell. The increased serum level of soluble transferrin receptor (sTfR) may indicate an abnormal intracellular distribution of iron and a decrease in the cytoplasmic compartment. Objective Our objective is to assess the possible role of iron metabolism dysfunction in the pathogenesis of MS. Methods Thirty subjects were selected from the Neurology Department of Kasr El-Aini hospital, Cairo University: 20 MS patients, where nine patients were relapsing and progressive (secondary progressive (SP) of which six were secondary progressive active (SP-A) and three were secondary progressive stable (SP-S)), seven were relapsing–remitting active (RR-A) and four were primary progressive (PP); and 10 control subjects matched in age and sex. Each patient was subjected to a thorough general medical and neurological examination, Kurtzke MS rating scales, laboratory assessment, neuro-imaging, evoked potentials and quantitative determination of the indices of iron metabolism, such as serum iron and sTfR. Results The serum level of sTfR was significantly higher in our MS patients compared with the control group ( p = 0.0001). The levels were significantly higher in SP-A ( p = 0.001), SP-S ( p = 0.01), RR-A ( p = 0.0001) and PP ( p = 0.003) patients than in controls. Iron values were within normal limits in all patients. The increased serum sTfR level in non-anemic MS patients with active disease reflects the increased iron turnover. The elevation of sTfR levels in stable patients may indicate active inflammation with ongoing oxidative damage that is not detectable by history or examination. Conclusions Iron overload and upregulation of iron-handling proteins, such as TfR, in the MS brain can contribute to pathogenesis of Multiple Sclerosis and iron imbalance is associated with a prooxidative stress and a proinflammatory environment, this suggest that iron could be a target for MS therapy to improve neuronal iron metabolism.

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Correlation between DJ-1 levels in the cerebrospinal fluid and the progression of disabilities in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458508093616 ◽

2008 ◽

Vol 14 (8) ◽

pp. 1056-1060 ◽

Cited By ~ 28

Author(s):

M Hirotani ◽

C Maita ◽

M Niino ◽

SM Iguchi-Ariga ◽

S Hamada ◽

...

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Healthy Subjects ◽

Significant Positive Correlation ◽

Healthy Controls ◽

Significant Difference ◽

Relapsing Remitting ◽

Multiple Sclerosis Patients

Objectives DJ-1 plays a key role in the anti-oxidative stress function. Increasing evidence supports the role of oxidative stress in the pathogenesis of multiple sclerosis (MS). The aim of this study was to investigate whether the DJ-1 levels were increased in patients with MS and to examine its association with the progression of MS. Methods Quantitative immunoblot assays were performed to evaluate the DJ-1 level in serum and cerebrospinal fluid (CSF) collected from relapsing–remitting patients with MS ( n = 29), disease controls subjects ( n = 14), and healthy subjects ( n = 44). Results No significant difference was observed in the serum DJ-1 level among the patients with MS, disease controls, and healthy controls. However, the CSF DJ-1 levels were significantly higher in the patients with MS than in the disease control subjects ( P < 0.0001). A significant positive correlation was also found between the CSF DJ-1 levels and the Multiple Sclerosis Severity Score ( P < 0.005, r = 0.501). Conclusions These results show that the CSF DJ-1 levels are significantly increased in the CSF of patients with MS and that the CSF DJ-1 levels may be associated with the disease progression of MS. Therefore, DJ-1 possibly plays an important role in the pathogenesis of MS.

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Myelin basic protein-like material in the urine of multiple sclerosis patients: relationships to clinical and neuroimaging changes

Multiple Sclerosis Journal ◽

10.1177/135245859800400329 ◽

1998 ◽

Vol 4 (3) ◽

pp. 243-246 ◽

Cited By ~ 3

Author(s):

John N Whitaker

Keyword(s):

Multiple Sclerosis ◽

Myelin Basic Protein ◽

Clinical Utility ◽

Basic Protein ◽

Progressive Multiple Sclerosis ◽

Group Data ◽

Relapsing Remitting ◽

Cryptic Epitope ◽

Multiple Sclerosis Patients

Urinary myelin basic protein-like material (MBPLM) represents material which is cross-reactive with a cryptic epitope in peptide 84-89 of human myelin basic protein. While normally present at moderate levels in the adult, these levels rise higher in patients who have secondary progressive multiple sclerosis (MS). The increase in urine MBPLM correlates with the burden of disease detected by T2-weighted cranial magnetic resonance imaging. There is no correlation between urinary MBPLM and acute disease activity in relapsing-remitting MS. The first major need for improving the clinical utility of measurements of MBPLM in urine in MS patients is to delineate its exact chemical features so that assays may be improved and a potential biological role of the MBPLM better understood. The second major task is to apply the group data accumulated and apply them to individual patients. This could prove to be means to individually direct treatment and determine its effectiveness.

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