Differential Expression of Cytokine-Coding Genes among Migraine Patients with and without Aura and Normal Subjects

Taheri, Mohammad; Nicknafs, Fwad; Hesami, Omid; Javadi, Alireza; Arsang‐Jang, Shahram; Sayad, Arezou; Ghafouri‐Fard, Soudeh

doi:10.1007/s12031-020-01745-y

Cited by 18 publications

(20 citation statements)

References 19 publications

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“…Tumor necrosis factor α (TNF-α) was elevated during attack in migraine patients with aura, and baseline levels were increased in general migraine patients. A 2021 study measured cytokine levels in the blood in migraine patients and healthy controls and discovered that TNF-α was elevated, but IL1-β was not compared to controls ( 41 ). Cerebrospinal fluid (CSF) protein measurements indicate that migraine patients have significantly different levels of transforming growth factor beta (TGF-β) 1, interleukin-1 receptor antagonist and monocyte chemoattractant protein 1 compared to controls ( 42 ).…”

Section: Clinical Evidence Of the Immune System Dysregulation In Migr...mentioning

confidence: 99%

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Dural Immune Cells, CGRP, and Migraine

Balcziak

Russo

2022

Front. Neurol.

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Migraine is the most common neurological disorder in the world, affecting 12% of the population. Migraine involves the central nervous system, trigeminal nerves and meninges. Recent advances have shown that targeting calcitonin gene-related peptide (CGRP) through either antibodies or small molecule receptor antagonists is effective at reducing episodic and chronic migraine episodes, but these therapeutics are not effective in all patients. This suggests that migraine does not have a singular molecular cause but is likely due to dysregulated physiology of multiple mechanisms. An often-overlooked part of migraine is the potential involvement of the immune system. Clinical studies have shown that migraine patients may have dysregulation in their immune system, with abnormal plasma cytokine levels either during the attack or at baseline. In addition, those who are immunocompromised appear to be at a higher risk of migraine-like disorders. A recent study showed that migraine caused changes to transcription of immune genes in the blood, even following treatment with sumatriptan. The dura mater is densely packed with macrophages, mast and dendritic cells, and they have been found to associate with meningeal blood vessels and trigeminal afferent endings. Recent work in mice shows activation and morphological changes of these cells in rodents following the migraine trigger cortical spreading depression. Importantly, each of these immune cell types can respond directly to CGRP. Since immune cells make up a large portion of the dura, have functional responses to CGRP, and interact with trigeminal afferents, CGRP actions on the dural immune system are likely to play key roles in migraine.

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Section: Clinical Evidence Of the Immune System Dysregulation In Migr...mentioning

confidence: 99%

“…It is important to note that this is within the confines of the CNS, vs. peripheral blood levels that the previous studies have represented. Finally, while cytokine dysfunction in migraine is indicated by numerous studies, there are conflicting reports ( 39 , 41 ).…”

Section: Clinical Evidence Of the Immune System Dysregulation In Migr...mentioning

confidence: 99%

Dural Immune Cells, CGRP, and Migraine

Balcziak

Russo

2022

Front. Neurol.

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“…Taheri et al . [ 89 ] compared the expressions of RNA-coding genes of IL-2, IL-4, CXCL8, IL-17, IFN-γ, TGF-β, and TNF-α cytokines in blood specimens of patients with migraine and those of healthy controls in order to identify any possible dysregulation. The authors reported that the expressions of RNA-coding genes of INF-γ, IL-4, TGF-β, and TNF-α were significantly increased from a statistical point of view in migraine cases, especially in males.…”

Section: Cytokine Levels In Migraineursmentioning

confidence: 99%

Immunological findings in patients with migraine and other primary headaches: a narrative review

Biscetti

Vanna

Cresta

et al. 2021

Clinical and Experimental Immunology

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Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the Human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine. The present review summarizes available findings to date from genetic and biomarker studies that have explored the role of inflammation in primary headaches.

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“…Migraine is a complex disorder with possible immunologic background (Bruno et al, 2007 ). We have recently reported over-expression of INF-γ, IL-4, TGF-β, and TNF-α, while down-regulation of CXCL8 in migraineurs compared with controls (Taheri et al, 2021 ). Moreover, we have demonstrated down-regulation of two members of protein inhibitor of activated STAT (PIAS) family in these patients (Ghafouri-Fard et al, 2021 ), further suggesting the abnormal immune homeostasis among migraineurs.…”

Section: Discussionmentioning

confidence: 97%

“…In the current study, we showed down-regulation of SOCS1–3 and SOCS5 in migraineurs compared with healthy controls. SOCS1 has been shown to be an important inhibitor of INF-γ signaling (Alexander et al, 1999 ), a cytokine which is up-regulated in migraineurs (Taheri et al, 2021 ). Down-regulation of SOCS1/3 has been shown to promote the expression of IFN-α/β in oligodendroglial cells (Li et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Expression Analysis of SOCS Genes in Migraine

Ghafouri‐Fard

Tamizkar

Sayad

et al. 2021

Front. Mol. Neurosci.

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Migraine is a complex neurological condition affecting a large proportion of persons. Dysregulation of several immune-related transcripts has been noted in migraineurs suggesting an immune-based background for this condition. We measured expression levels suppressor of cytokine signaling (SOCS) genes in the venous blood of migraineurs compared with controls. SOCS1 was down-regulated in patients without aura compared with controls [Ratio of mean expression (RME) = 0.08, P value < 0.001]. This pattern was also detected among female subgroups (RME = 0.06, P value = 0.010), but not among male subgroups (RME = 0.22, P value = 0.114). Expression of SOCS1 was significantly higher in patients with aura compared with those without aura (RME = 5.89, P value = 0.037). Meanwhile, expression of SOCS2 was lower in migraineurs with aura compared with controls (RME = 0.03, P value < 0.001). In addition, this gene was under-expressed in patients without aura compared with controls and in both sex-based subgroups of this group of patients (RME = 0.01, P value < 0.001 for all comparisons). However, its expression was higher in male patients with aura compared with those without aura (P value < 0.001). For SOCS3, we detected a lower level of expression in patients without aura compared with controls (RME = 0.07, P value < 0.001). However, the expression of SOCS3 was higher in patients with aura compared with those without aura (RME = 7.46, P value = 0.001). SOCS5 was down-regulated in patients without aura compared with controls (RME = 0.10, P value < 0.001). Expression of this gene was also lower in patients with aura compared with controls (RME = 0.03, P value < 0.001), and in male patients of this group compared with controls (RME = 0.03, P value = 0.004). On the other hand, expression of SOCS5 was higher in male patients with aura compared with sex-matched patients without aura (RME = 6.67, P value = 0.001). SOCS2 levels could appropriately differentiate migraineurs from healthy subjects. The current study suggests the role of SOCS genes in the pathoetiology of migraine.

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Differential Expression of Cytokine-Coding Genes among Migraine Patients with and without Aura and Normal Subjects

Cited by 18 publications

References 19 publications

Dural Immune Cells, CGRP, and Migraine

Dural Immune Cells, CGRP, and Migraine

Immunological findings in patients with migraine and other primary headaches: a narrative review

Expression Analysis of SOCS Genes in Migraine

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