Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development

Kivisäkk, Pia; Healy, Brian C.; Francois, Katiana; Gandhi, Roopali; Gholipour, Taha; Egorova, Svetlana; Sevdalinova, Velina; Quintana, Francisco J.; Chitnis, Tanuja; Weiner, Howard L.; Khoury, Samia J.

doi:10.1177/1352458513503052

Cited by 41 publications

(40 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Osteopontin is present at elevated levels in the plasma of MS patients compared with healthy control subjects [Kivisäkk et al 2014], and at elevated levels in the CSF of MS patients compared with patients with other neurological diseases . Osteopontin is expressed in the lesions of progressive MS patients and has been found to be elevated in the blood [Hur et al 2007] and CSF [Szalardy et al 2013] of MS patients during relapse, decreasing significantly during recovery from relapse [Börnsen et al 2011].…”

Section: Other Effects Of Natalizumab In Rrmsmentioning

confidence: 98%

“…Osteopontin is expressed in the lesions of progressive MS patients and has been found to be elevated in the blood [Hur et al 2007] and CSF [Szalardy et al 2013] of MS patients during relapse, decreasing significantly during recovery from relapse [Börnsen et al 2011]. Natalizumab treatment has been shown to decrease osteopontin levels in the CSF ] and plasma [Kivisäkk et al 2014] of RRMS patients. In a study of RRMS patients receiving natalizumab for 2 years, mean plasma osteopontin levels decreased by approximately 31% (p < 0.005), and this decrease correlated with significant (p < 0.005) improvements in mean global cognitive impairment index values [Iaffaldano et al 2014].…”

Section: Other Effects Of Natalizumab In Rrmsmentioning

confidence: 99%

See 1 more Smart Citation

Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

Sellebjerg

Cadavid

Steiner

et al. 2015

Ther Adv Neurol Disord

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial.

show abstract

Section: Other Effects Of Natalizumab In Rrmsmentioning

confidence: 98%

Section: Other Effects Of Natalizumab In Rrmsmentioning

confidence: 99%

Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

Sellebjerg

Cadavid

Steiner

et al. 2015

Ther Adv Neurol Disord

View full text Add to dashboard Cite

show abstract

“…For its action in the regulation of immune system, OPN has been recognized to have a role in the development/progression of several autoimmune diseases, such as multiple sclerosis (16,17,18,19) rheumatoid arthritis (20,21), psoriasis (22) and Graves' disease (23).…”

Section: Introductionmentioning

confidence: 99%

Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile

Barchetta¹,

Alessandri

Bertoccini³

et al. 2016

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Osteopontin (OPN) is a sialoprotein implicated in different immunity and metabolic pathways. Capable of activating dendritic cells and inducing Th1-Th17-mediated tissue damage, OPN plays a significant role in the development/progression of several autoimmune diseases; interestingly, it was also shown that OPN participates in the acute pancreatic islets response to experimentally induced diabetes in non-obese diabetic (NOD) mice. Furthermore, OPN promotes adipose tissue dysfunction, systemic inflammation and insulin resistance. Our aims of this study were to evaluate circulating OPN levels in adult patients with type 1 diabetes mellitus (T1DM) compared to non-diabetic control participants and to unravel clinical and biochemical correlates of OPN concentration. Design: Case-control study. Methods: We enrolled 54 consecutive T1DM patients referred to our diabetes outpatient clinic at Sapienza University of Rome and 52 healthy sex and age-comparable controls. The study population underwent clinical evaluation, blood sampling for biochemistry and complete screening for diabetes complications. Serum OPN levels were measured by MILLIPLEX Multiplex Assays Luminex. Results: T1DM patients had significantly higher serum OPN levels than controls (17.2G12.9 vs 10.5G11.6 mg/ml, PZ0.009). OPN levels correlated with T1DM, higher blood pressure, BMI, creatinine, g-GT, ALP and lower HDL; the association between high OPN levels and T1DM was independent from all confounders. No correlation was shown between OPN and HbA1c, C-peptide, insulin requirement, co-medications and diabetes duration. Conclusions: This study demonstrates for the first time in a case-control study that adults with T1DM have increased serum OPN levels, and that higher OPN concentrations are associated with an unfavorable metabolic profile in these patients.

show abstract

“…Moreover, OPN level correlated positively with disease activity and relapse rate [50][51][52][53]. However, there are studies which showed that higher OPN serum level in MS patients is not associated with disease severity [54,55].…”

Section: Multiple Sclerosismentioning

confidence: 92%

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

Kaleta¹

2017

Genetic Polymorphisms

View full text Add to dashboard Cite

Osteopontin (OPN) is a pleiotropic protein, important in bone remodeling and immune system signaling. OPN is synthesized in a variety of cells and tissues. It can be found not only in bone cells but also in immune cells (B and T lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, macrophages, neutrophils, and dendritic cells). OPN regulates T-helper 1/T-helper 2 (Th1/Th2) balance, stimulates B cells to antibodies production, regulates macrophages and neutrophils function, and activates dendritic cells. A number of factors, including hormones, cytokines, and polymorphisms of promoter region of OPN gene, regulate protein expression. OPN and variants of the OPN gene have been associated with the pathogenesis of multiple disorders, including systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, systemic sclerosis, inlammatory bowel diseases, asthma, type 1 diabetes, and many other. However, some studies gave diferent or inconclusive results. Thus, the role of OPN polymorphic variants in autoimmune diseases needs to be beter deined and explored as a diagnostic and therapeutic target to monitor and treat immune-mediated conditions.

show abstract

Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development

Abstract: Our data do not support a role for circulating OPN levels as a biomarker for disease activity in a heterogeneous clinical setting, but does not rule out a potential role in the cerebrospinal fluid, in a controlled setting such as a clinical trial, or in concert with other biomarkers.

Cited by 41 publications

References 32 publications

Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

Contact Info

Product

Resources

About