Matrix Metalloproteinases in Myasthenia Gravis

Helgeland, Geir; Petzold, Axel; Luckman, Steven P.; Gilhus, Nils Erik; Plant, Gordon T.; Romi, Fredrik

doi:10.1159/000322737

Cited by 17 publications

(14 citation statements)

References 67 publications

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“…It was not possible to correlate MMP-3-positive patients with a specific subset of MG patients, perhaps due to low number of MMP-3-positive MG patients and large variation in disease entities. A similar subgroup with high MMP-3 levels in another MG cohort was recently reported, containing GMG, OMG, SPMG, and SNMG patients [20]. …”

Section: Discussionsupporting

confidence: 68%

Matrix Metalloproteinase-3 in Myasthenia Gravis Compared to Other Neurological Disorders and Healthy Controls

Luckman

Gilhus²,

Romi

2011

Autoimmune Diseases

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MMP-3 is capable of degrading a variety of proteins, including agrin, which plays a critical role in neuromuscular signaling by controlling acetylcholine receptor clustering. High MMP-3 levels in a proportion of myasthenia gravis (MG) patients have been reported. A pathogenic role of MMP-3 in other neurological disorders has been suggested but not proven. We have therefore examined the levels of MMP-3 in 124 MG patients and compared them to 59 multiple sclerosis (MS) patients, 74 epilepsy patients, 33 acute stroke patients, and 90 healthy controls. 15.3% of the patients in the MG group were MMP-3-positive (defined as higher than cutoff value 48 ng/mL) with very high mean MMP-3 concentration (79.9 ng/mL), whereas the proportion of MMP-3 positive patients in the MS (3.4%), epilepsy (6.7%), stroke (0%), and the control group (4.4%) was significantly lower. Mean MMP-3 concentration in the total MG group (25.5 ng/mL) was significantly higher than in the MS (16.6 ng/mL) and stroke (11.7 ng/mL) groups, but did not differ significantly from the epilepsy (19.4 ng/mL) and the control group (23.4 ng/mL). MMP-3 may have a specific pathogenic effect in MG in addition to being associated with autoimmune diseases in general.

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Section: Discussionsupporting

confidence: 68%

Matrix Metalloproteinase-3 in Myasthenia Gravis Compared to Other Neurological Disorders and Healthy Controls

Luckman

Gilhus²,

Romi

2011

Autoimmune Diseases

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“…Elevated serum MMP-3 levels are present in both SPMG and SNMG [52]. High serum MMP-3 levels were confirmed in another MG cohort, where the patients had OMG or MG with ocular muscle predominance [53]. Interestingly, in this cohort, females had significantly lower serum MMP-3 concentrations than males, and male patients were overrepresented among those with higher serum MMP-3 concentrations (male:female ratio = 4:1).…”

Section: Serum Levels Of Mmps In Mgmentioning

confidence: 79%

Serum Levels of Matrix Metalloproteinases: Implications in Clinical Neurology

Romi

Helgeland²,

Gilhus³

2012

Eur Neurol

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Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in remodeling extracellular matrix and cell-matrix interactions. A pathogenic role of MMPs in neurological disorders is likely. This paper focuses on serological clinical aspects only. In multiple sclerosis, higher serum MMP-3 is seen during relapses. Lower serum MMP-8 and -9 levels correlate with fewer contrast-enhanced T₂-weighted MRI lesions, and serum MMP-9 can be used in monitoring treatment. In myasthenia gravis, serum MMP-2, -3, and -9 levels are elevated in both generalized and ocular diseases. A proportion of the patients have markedly increased serum MMP-3. In acute stroke, higher serum MMP-9 correlates with larger infarct volume, stroke severity, and worse functional outcome, and serum MMP-3 is significantly lower than in several other neurological disorders and healthy controls. In amyotrophic lateral sclerosis, serum MMP-2 correlates with disease progression, and both serum MMP-1 and -2 are elevated. In Alzheimer’s disease, serum MMP-3, -9, and -10 are elevated. In migraine, serum MMP-2 is elevated, and also MMP-9 in those patients with migraine without aura. MMP-9 is implicated in the pathogenesis of experimental epilepsy. A pathogenic role of MMPs in these conditions could be related to their ability to degrade extracellular matrix. MMPs may also facilitate autoimmunity.

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“…MMP sex effects have also been reported in postmyocardial infarction patients, as well as controls, with MMP‐3 blood levels significantly higher in males compared with females . The observed difference of MMP‐3 between sexes was previously described in myasthenia gravis (MG), but there was no correlation with MG subtype, and the possible reason for this difference was not discussed …”

Section: Discussionmentioning

confidence: 83%

Plasma matrix metalloproteinase-3 correlates with the clinical severity in men with multiple system atrophy

Sasaki

Matsushima

Hama

et al. 2013

Neurol Clin Neurosci

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Aim Matrix metalloproteinase‐3 (MMP‐3), MMP‐9 and tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) play roles in remodeling and repairing tissue. The aim of the present study was to investigate correlations between plasma levels of these proteins and clinical severity of multiple system atrophy (MSA). Methods MMP‐3, MMP‐9 and TIMP‐1 levels were measured by enzyme‐linked immunosorbent assay (ELISA) in 72 MSA patients and 48 adult controls. Clinical severity was rated with the scale for assessing and rating ataxia (SARA) and the unified MSA rating scale (UMSARS). Immunohistochemistry and immunoblotting were used to assess MMP‐3 expression in post‐mortem brain tissue. Results Plasma MMP‐3 was significantly lower in females than males, but MMP‐9 and TIMP‐1 showed no sex difference. Compared with age‐matched controls (age ≥40 years), male MSA patients had significantly lower plasma MMP‐3, but no difference was detected in female MSA patients versus controls. We observed significant correlations with rating scales in male, but not female, patients; plasma TIMP‐1 positively correlated with SARA and UMSARS, whereas plasma MMP‐3 showed an inverse correlation with the rating scales. These correlations became more evident when the MMP‐3/TIMP‐1 ratio was used as an index. Plasma MMP‐9 did not correlate with any scales in male patients, but was positively correlated with UMSARS in female patients. Immunohistochemical studies of post‐mortem brain tissues showed that total cerebellar MMP‐3 expression was not significantly different between MSA patients and controls, but glial cytoplasmic inclusions were intensely immunoreactive for MMP‐3. Conclusion MMP‐3 and TIMP‐1 are possible biomarker candidates for MSA. However, it is unclear whether they accurately reflect clinical progression.

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Matrix Metalloproteinases in Myasthenia Gravis

Cited by 17 publications

References 67 publications

Matrix Metalloproteinase-3 in Myasthenia Gravis Compared to Other Neurological Disorders and Healthy Controls

Matrix Metalloproteinase-3 in Myasthenia Gravis Compared to Other Neurological Disorders and Healthy Controls

Serum Levels of Matrix Metalloproteinases: Implications in Clinical Neurology

Plasma matrix metalloproteinase-3 correlates with the clinical severity in men with multiple system atrophy

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