Serum cytokine levels do not correlate with disease activity and severity assessed by brain MRI in multiple sclerosis

Objective.Endoplasmic reticulum aminopeptidase (ERAP)1 is associated with ankylosing spondylitis (AS) and is known to be involved in the clipping of the cytokine receptors interleukin 1 receptor II (IL-1RII), IL-6Rα, and tumor necrosis factor receptor I (TNFRI). We studied the relationship of these serum cytokine receptors and their corresponding cytokines to markers of inflammation and polymorphisms in ERAP1 and ERAP2 in patients with AS.Methods.Sera from patients with AS were assayed for TNF-α, IL-1, IL-6, sTNFRI, sIL-1RII, and sIL-6Rα by ELISA. Genotyping was performed for 3 AS-associated nonsynonymous single-nucleotide polymorphisms in the ERAP1 gene [rs27044(C/G), rs10050860(C/T), and rs30187(C/T)] and 1 in the ERAP2 gene [rs2549782(T/G)]. The serum cytokine and receptor levels were compared between the different genotype groups and correlated to markers of inflammation and disease activity.Results.Eighty patients with AS (21 women) with a mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 5.3 ± 2.4 were enrolled. There was a significant correlation of sTNFRI with C-reactive protein (CRP; R = 0.43, p < 0.001) and erythrocyte sedimentation rate (ESR; R = 0.30, p = 0.01) but not with BASDAI. Serum cytokine levels were undetectable in the majority of patients. There was no significant difference in serum cytokines or the soluble receptors between patients with the different ERAP1/ERAP2 polymorphisms and their haplotypes. Similarly, there was no relationship of the polymorphisms with the serum cytokine levels nor the cytokine-receptor ratio.Conclusion.Soluble TNFRI levels correlate with ESR and CRP in AS. The ERAP1 and ERAP2 polymorphisms associated with AS do not influence the serum cytokine receptor levels in patients with AS.

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Patterns of disease activity in multiple sclerosis patients: A study with quantitative gadolinium-enhanced brain MRI and cytokine measurement in different clinical subgroups

Journal of Neurology ◽

10.1007/bf00886876 ◽

1996 ◽

Vol 243 (7) ◽

pp. 536-542 ◽

Cited By ~ 25

Author(s):

Marco Rovaris ◽

David Barnes ◽

Nicola Woodrofe ◽

George H. du Boulay ◽

John W. Thorpe ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Brain Mri ◽

Multiple Sclerosis Patients ◽

Cytokine Measurement

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060 Association of brain volume loss and neda outcomes in patients with relapsing multiple sclerosis in the opera i and opera ii studies (ENCORE)

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.59 ◽

2018 ◽

Vol 89 (6) ◽

pp. A25.1-A25

Author(s):

Anthony Traboulsee ◽

Douglas Arnold ◽

Eric C Klawiter ◽

Eva Havrdova ◽

Damian Fiore ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Brain Tissue ◽

Repeated Measures ◽

Brain Volume ◽

Brain Mri ◽

Treatment Goal ◽

Volume Loss ◽

T2 Lesions ◽

Brain Volume Loss

IntroductionBrain volume loss (BVL) occurs in multiple sclerosis (MS) patients, reflecting irreversible tissue damage. No evidence of disease activity (NEDA), a composite measure assessing absence of clinical and magnetic resonance imaging (MRI) disease activity has emerged as important treatment goal in MS and may be associated with preservation of brain tissue and BVL prevention.MethodsPatients in OPERA-I/II (NCT01247324/NCT01412333) received 600 mg ocrelizumab (intravenous) very 24 weeks or 44 µg subcutaneous interferon beta-1a (IFNβ-1a) 3x-weekly for 96 weeks. Brain MRI assessments were completed at baseline and 24/48/96 Weeks. Brain volume normalised for head size was measured using SIENAX software. Percent change in whole brain volume (WBV) was determined using SIENA software, changes in cortical grey (GMV) and white (WMV) matter volumes were measured using validated, locally developed Jacobian integrator atrophy software. NEDA was defined as absence of relapses, 12-week confirmed disability progression, T1 Gd–enhancing lesions and new and/or enlarging T2-lesions. Changes from baseline in brain volume were examined in NEDA patients and those with evidence of disease activity (EDA), using the mixed-effects model for repeated measures method.ResultsThe analysis included 1520 patients (ocrelizumab-761; IFNβ-1a-759). Over 96 weeks, 569 (37%) patients [ocrelizumab-363 (48%); IFNβ-1a-206(27%); p<0.001] had NEDA. Compared with EDA patients, NEDA patients had significantly less WBV loss from baseline (30%-reduction; p<0.001). In the NEDA group, ocrelizumab patients had significantly less WBV loss (32%-reduction; p<0.001), WMV loss (34%-reduction; p=0.044) and GMV loss (30%-reduction; p<0.001) from baseline than IFNβ-1a patients. In the EDA group, ocrelizumab patients had significantly less WBV loss (11%-reduction; p=0.047) and GMV loss (21%-reduction; p<0.001) but not WMV loss (1.03%-increase; p=0.90) from baseline than IFNβ-1a patients.ConclusionThese findings highlight the importance of NEDA as treatment goal with respect to brain tissue preservation regardless of treatment choice. Ocrelizumab may confer additional benefits in NEDA patients NEDA beyond what is observed with IFNβ-1a.

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Th17 cells: A prognostic marker for MS rebound after natalizumab cessation?

Multiple Sclerosis Journal ◽

10.1177/1352458516640609 ◽

2016 ◽

Vol 23 (1) ◽

pp. 114-118 ◽

Cited By ~ 13

Author(s):

Jürgen Haas ◽

Katharina Schneider ◽

Alexander Schwarz ◽

Mirjam Korporal-Kuhnke ◽

Simon Faller ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Prognostic Marker ◽

Peripheral Blood ◽

Th17 Cell ◽

Th17 Cells ◽

T Helper ◽

T Helper 17 ◽

Blood Samples ◽

Cytokine Levels

Background: Multiple sclerosis (MS) patients are at risk of renewed disease activity after discontinuing natalizumab (NAT) treatment. Objective: Assessing the implication of T helper 17 (Th17) cells in MS reactivation after NAT cessation. Methods: We monitored frequencies of Th17 cells and interleukin (IL)-17 cytokine levels in blood samples of 57 MS patients, without, during, and after NAT exposure. Results: Frequencies of both Th17 cells and, in part, also IL-17 levels, in peripheral blood increased under prolonged NAT therapy, returned to baseline after NAT withdrawal and became almost undetectable in blood samples of individuals who experienced relapses during the wash-out phase. Conclusion: Assessing the Th17-cell/IL-17 axis might help to predict rebound MS activity after NAT withdrawal.

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Onset of clinical and MRI efficacy of ocrelizumab in relapsing multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000008189 ◽

2019 ◽

Vol 93 (19) ◽

pp. e1778-e1786 ◽

Cited By ~ 11

Author(s):

Frederik Barkhof ◽

Ludwig Kappos ◽

Jerry S. Wolinsky ◽

David K.B. Li ◽

Amit Bar-Or ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Phase Ii ◽

Relapse Rate ◽

Phase Ii Study ◽

Brain Mri ◽

Clinical Disease ◽

Phase Iii ◽

Phase Iii Studies ◽

Relapsing Multiple Sclerosis

ObjectiveTo assess the onset of ocrelizumab efficacy on brain MRI measures of disease activity in the phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled phase III studies in relapsing multiple sclerosis (RMS).MethodsBrain MRI activity was determined in the phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) β-1a (30 μg). Annualized relapse rate (ARR; over various epochs) and time to first relapse were analyzed in the pooled population of the phase III OPERA (A Study of Ocrelizumab in Comparison With Interferon Beta-1a [Rebif] in Participants With Relapsing Multiple Sclerosis) I and OPERA II trials in patients with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN-β-1a (44 μg).ResultsIn patients with RRMS, ocrelizumab reduced the number of new T1 gadolinium-enhancing lesions by week 4 vs placebo (p = 0.042) and by week 8 vs intramuscular IFN-β-1a (p < 0.001). Ocrelizumab also reduced the number of new or enlarging T2 lesions appearing between weeks 4 and 8 vs both placebo and IFN-β-1a (both p < 0.001). In patients with RMS, ocrelizumab significantly reduced ARR (p = 0.005) and the probability of time to first protocol-defined relapse (p = 0.014) vs subcutaneous IFN-β-1a within the first 8 weeks.ConclusionEpoch analysis of MRI-measured lesion activity in the phase II study and relapse rate in the phase III studies consistently revealed a rapid suppression of acute MRI and clinical disease activity following treatment initiation with ocrelizumab in patients with RRMS and RMS, respectively.Classification of evidenceThis study provides Class II evidence that for patients with RRMS and RMS, ocrelizumab suppressed MRI activity within 4 weeks and clinical disease activity within 8 weeks.

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Long-term Reduction in Brain MRI Disease Activity and Atrophy after 5 years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2018.10.104 ◽

2018 ◽

Vol 26 ◽

pp. 265 ◽

Cited By ~ 1

Author(s):

D.L. Arnold ◽

L. Kappos ◽

S.L. Hauser ◽

X. Montalban ◽

A. Traboulsee ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Brain Mri ◽

Relapsing Multiple Sclerosis

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Decreased Cerebrospinal Fluid Antioxidative Capacity Is Related to Disease Severity and Progression in Early Multiple Sclerosis

Biomolecules ◽

10.3390/biom11091264 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1264

Author(s):

Margarete M. Voortman ◽

Anna Damulina ◽

Lukas Pirpamer ◽

Daniela Pinter ◽

Alexander Pichler ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Disease Activity ◽

Neuronal Damage ◽

Brain Mri ◽

Time Interval ◽

Antioxidative Capacity ◽

Subclinical Disease ◽

Relapsing Remitting

Background: Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC). The relation of AOC to outcome measures in MS still remains inconclusive. We aimed to compare AOC in cerebrospinal fluid (CSF) and serum between early MS and controls and assess its correlation with clinical/radiological measures. Methods: We determined AOC (ability of CSF and serum of patients to inhibit 2,2′-azobis(2-amidinopropane) dihydrochloride-induced oxidation of dihydrorhodamine) in clinically isolated syndrome (CIS)/early relapsing-remitting MS (RRMS) (n = 55/11) and non-inflammatory neurological controls (n = 67). MS patients underwent clinical follow-up (median, 4.5; IQR, 5.2 years) and brain MRI at 3 T (baseline/follow-up n = 47/34; median time interval, 3.5; IQR, 2.1 years) to determine subclinical disease activity. Results: CSF AOC was differently regulated among CIS, RRMS and controls (p = 0.031) and lower in RRMS vs. CIS (p = 0.020). Lower CSF AOC correlated with physical disability (r = −0.365, p = 0.004) and risk for future relapses (exp(β) = 0.929, p = 0.033). No correlations with MRI metrics were found. Conclusion: Decreased CSF AOC was associated with increased disability and clinical disease activity in MS. While our finding cannot prove causation, they should prompt further investigations into the role of AOC in the evolution of MS.

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Effects of alfacalcidol therapy on serum cytokine levels in patients with multiple sclerosis

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh05s2124v ◽

2005 ◽

Vol 133 (Suppl. 2) ◽

pp. 124-128 ◽

Cited By ~ 3

Author(s):

Slobodan Vojinovic ◽

Jelena Vojinovic ◽

Vladan Cosic ◽

Vojin Savic

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Neurological Diseases ◽

Control Group ◽

Therapeutic Effects ◽

Serum Cytokine ◽

Immunomodulatory Agents ◽

Cytokine Levels ◽

High Doses ◽

Genetic And Environmental Factors

Multiple sclerosis (MS) is a consequence of genetic and environmental factors. Geographic, genetic, and biological evidence suggests that an important immunopathogenic factor might be the insufficiency of vitamin D. The aim of our study was to investigate the immunomodulatory effect of alfacalcidol, a vitamin D analogue, on cytokine levels in RRMS patients in relapse. We investigated 15 patients suffering from RRMS relapse (an RRMS group) and two control groups: one control group of healthy subjects (n=10) and a NIND group, consisting of patients with non-inflammatory neurological diseases (n=10). All of the MS patients were treated with 5 ?gr/day of oral alfacalcidol for a period of five days. The serum cytokine levels of TNF-?, IL-10, IL-4, and IL-12 were measured in all the MS patients one day prior to and one day after therapy, and in all the control subjects (ELISA, Quantikine human immunoassay, R&D Systems, UK). Our results showed significantly lower IL- 4 and IL- 12 levels in the RRMS patients group compared to the N group and the NIND group (p<0.001 Mann-Whitney U-test). No significant differences in TNF-? and IL-10 levels were found between the groups, and there was no influence of alfacalcidol on these cytokines in RRMS patients. High doses of oral alfacalcidol induced significant increases in IL-4 and IL-12 levels in RRMS patients (p<0.001, Wilcoxon rank signed test). Therefore, there were no differences in IL- 4 and IL- 12 levels compared to the N group and the NIND group. Alfacalcidol therapy in RRMS patients did not provoke any side effects. Vitamin D and its analogues, such as alfacalcidol, act as immunomodulatory agents, with potential therapeutic effects for patients with multiple sclerosis.

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Serum Leucine-Rich α2-Glycoprotein as a Biomarker for Monitoring Disease Activity in Patients with Systemic Juvenile Idiopathic Arthritis

Journal of Immunology Research ◽

10.1155/2019/3140204 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Masaki Shimizu ◽

Natsumi Inoue ◽

Mao Mizuta ◽

Yasuo Nakagishi ◽

Akihiro Yachie

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Disease Activity ◽

Influenza A ◽

Systemic Juvenile Idiopathic Arthritis ◽

C Reactive Protein ◽

Serum Cytokine ◽

Tumor Necrosis Factor Receptors ◽

Reactive Protein ◽

Cytokine Levels ◽

Necrosis Factor

To investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are useful as a marker of disease activity in systemic juvenile idiopathic arthritis (s-JIA), we determined serum LRG levels in fifty-nine s-JIA patients, 15 with other subtypes of JIA, 7 with Kawasaki disease (KD), 7 with influenza A infection (flu), 7 with enterohemorrhagic Escherichia coli (EHEC) infection, and 20 healthy controls (HC). Results were compared with the clinical features of s-JIA and serum cytokine levels including interleukin- (IL-) 6, IL-18, and soluble tumor necrosis factor receptors I and II. Serum LRG levels in active s-JIA were higher compared to those in other subtypes of JIA, EHEC, flu patients, and HC. Serum LRG levels were normalized in the inactive s-JIA phase after treatment. Serum LRG levels were positively correlated with serum C-reactive protein and ferritin levels. Serum LRG levels reflected s-JIA disease activity and thus may be useful for monitoring s-JIA disease activity.

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