Increased autotaxin activity in MS




Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA) from lysophosphatidyl choline (LPC) and it is up-regulated in inflammatory conditions such as various cancers, arthritis and multiple sclerosis (MS). Numerous studies have shown that the LPA signaling gives rise to angiogenesis, mitosis, cell proliferation and cytokine secretion. On the one hand, an increasing body of evidence suggests that blockade of ATX has anti-inflammatory properties in a variety of diseases.

The aim of this study was to measure the enzyme activity of ATX in cerebro-spinal fluid (CSF) and serum of patients with MS using an enzymatic photometric method. 20 patients with active relapsing–remitting MS were enrolled. None had received any immune modulator, immunosuppressive treatment and vitamin D supplement within the six preceding months.

In addition to the active MS patients, 20 age and sex matched patients with other neurological diseases (OND) without any CNS demyelinating lesions on their MRI were selected as a control group. The control group consisted of patients with seven benign intracranial hypertension, five with epilepsy, three with headache, two with normal pressure hydrocephalus, two with motor neuron disease and one with cerebral venous sinus thrombosis. CSF samples were taken by lumbar puncture (LP) for diagnostic purposes.

At least 1 ml of CSF was obtained from each patient by non-traumatic LP. CSF samples were collected from MS patients exclusively during the clinical relapse (active) phase of the disease (within two weeks of the onset of acute or sub-acute exacerbation). CSF samples were immediately centrifuged at 800 rpm, at 4°C for five minutes, and the supernatants were stored at −80 °C until measurement. They were also screened for possible systemic infection in order to avoid false positive ATX activity.

After an overnight fast, blood was collected from 20 patients with multiple sclerosis (relapsing–remitting) and from 20 controls. Serum was drawn off after the collected blood had been left for an hour at room temperature and then spun at 2500 rpm for 15 minutes. Samples were stored at −20 °C until the measurement of ATX and more than one freeze thaw cycle was avoided. Measurement of ATX was done on CSF and serum of two selected groups. The results showed that ATX activity was significantly higher in MS patients than those patients diagnosed with OND. This was the first report of high activity of the ATX enzyme in the CSF of MS patients and further studies are needed to shed light on the enzymatic role of ATX in disease pathobiology.

Authors: Zahednasab H, Balood M
Source: J Neuroimmunol. 2014 Jun 19. pii: S0165-5728(14)00177-5. doi: 10.1016/j.jneuroim.2014.06.006. [Epub ahead of print]
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