T-cell pointed to Parkinson’s disease before symptoms appear

T cells specific for the protein alpha synuclein that accumulates in Parkinson’s disease may be a marker of disease development before the onset of symptoms. The researchers studied blood samples of a patient with Parkinson’s disease, which had been stored frozen for two decades, as well as analyses of a group of people with the same disease. Cells specific for the alpha synuclein, often found in patients years before the diagnosis, and in other patients in the first few years of treatment. Article published in the journal Nature Communications.

Parkinson’s disease is clinically diagnosed only when they begin to show motor dysfunction. Motor stage preceded by two stages of disease development: pre-clinical, which does not manifest itself externally, and with prodromal non-motor symptoms. In the second stage, the disease can be seen in several manifestations: constipation, decreased sense of smell, volatile mood and disorder of the paradoxical phase of sleep. Symptoms are many and they can appear years before motor disturbances, but they are not sufficiently specific for the diagnosis of Parkinson’s disease.

At the cellular level Parkinson’s disease manifests itself in the destruction of dopaminergic neurons in the reticulate layer of the substantia nigra region of the midbrain. Within the first four years after diagnosis the number of neurons in this area is reduced by 50-90 percent and then ceases to change. Nerve cells can start to break even at the prodromal stage, long before diagnosis and start of treatment, which reduces the effectiveness of therapy. Therefore, the search for markers that can identify the disease in its early stages, important for the development of ways of its treatment.

A few years ago Alessandro Sette (Sette, Alessandro) University of California, San Diego contacted the patient with Parkinson’s disease. Coincidentally, in 1998, he regularly donated blood and the samples of mononuclear cells of peripheral blood were frozen. The patient read the previous study of the group of Alessandro Sette and decided that samples of his blood could come in handy.

In a previous work, the researchers studied the interaction of immune T cells with the protein fragments of the alpha synuclein that accumulates in neurons in Parkinson’s disease. These cells triggers autoimmune reaction to its own nerve cells.

With tests the patient performed the same manipulations as in the previous study. Mononuclear cells of peripheral blood within two weeks incubated with epitopes (pieces) of alpha-synuclein. Then with the help of fluorescent cells was determined by the number of antigen specific T cells for cytokine content (interferon gamma, interleukins 5 and 10). The same is done with the samples from 97 volunteers with Parkinson’s disease and 67 healthy participants.

The reaction of T cells to alpha-synuclein was much higher before 2006 than after diagnosis (2009; p = 0.008) in the first patient. In General, people with Parkinson’s disease the amplitude of the response was significantly higher than in healthy volunteers (p < 0.0001). The strongest reaction of the T cells was in the first years after diagnosis and then decreased.

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