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Research reveals previously unappreciated immune processes associated with migraine

The doctoral dissertation of Dilyara Nurkhametova, MD, provides a novel view on the involvement of local and systemic inflammatory processes in migraine, which were previously little studied in this disorder. Thus, the findings reveal previously unappreciated immune processes associated with migraine.

Migraine is a common neurological disorder affecting every seventh person around the world and approximately 1 million people in Finland. Debilitating headache often accompanied with other neurological symptoms is the main clinical manifestation of migraine. Affecting mostly young people, migraine has a substantial social and economic impact and rated as one of the leading causes of disability in working-age population.

The role of local neuroinflammation in meninges was already suggested as one of the pathophysiological mechanisms in migraine. Given that mast cells are present in large amount in meninges, the researchers proposed that they are the important contributors to the local inflammatory processes and sensitization of pain afferents. In the first part of the study, they focused on the role of pro-inflammatory P2X7-receptors in the activation of meningeal mast cells. The stimulation of P2X7-receptors in these immune cells with the purinergic agonist, ATP, and the specific P2X7 agonist, BzATP, led to the specific large pore opening, which is a signature of this receptor subtype and associated with subsequent release of the pro-inflammatory cytokines.

In the second part of the study, the focus was on the role of the immune cells such as T lymphocytes in migraine. T lymphocytes are central players in systemic immune reactions and a common source of pro-nociceptive and pro-inflammatory cytokines. The researchers found that regulatory T cells (Tregs), which are responsible for limiting inflammation, express, in patients with migraine, a reduced level of the main ATP degrading enzymes CD39 and CD73. Thus, the results point to a double-edged disrupted purinergic signaling in migraine in these T cells. Interestingly, in functional terms, a deficit of CD39, which normally destroys pro-inflammatory ATP, is complimentary to a reduction in CD73, which deficiency limits the amount of anti-inflammatory adenosine. Thus, both of the effects associated with migraine shift the purinergic signalling towards the pro-inflammatory spectrum. Moreover, since CD39/CD73 pathway determines Tregs immune suppressive function, this finding suggests that the function of Tregs is malfunctioning in migraine.

In the third study, the researchers examined the other subset of T lymphocytes - helper T cells - and found that patients with migraine have an increased proportion of the pro-inflammatory Th17 cells, while the number of Th1 cells was diminished. In addition, they also revealed similar pro-inflammatory changes in follicular helper T cells, which are currently considered as important contributors to autoimmune disorders. These findings suggest that in migraine, there is a similar pro-inflammatory shift in the immune reactions as encountered in the autoimmune disorders.

These findings highlight novel aspects of migraine and suggest new possible targets for developing novel previously unappreciated therapeutics considering immunological pathophysiological mechanisms of this disorder.

The doctoral dissertation of Dilyara Nurkhametova, Doctor of Medicine, entitled The purinergic immune mechanisms of migraine: the role of mast cells and T cells, will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Antonio Cuadrado of the Autonomous University of Madrid, and the Custos will be Professor Rashid Giniatullin of the University of Eastern Finland.

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Nurkhametova, Dilyara. The purinergic immune mechanisms of migraine: the role of mast cells and T cells - Purinergic immunology of migraine