Flow Cytometric Analysis of Lymphocyte Subsets in Migraine Patients During and Outside of an Acute Headache Attack

Abstract

We have conducted flow cytometric studies of two subsets of lymphocyte markers in groups of migraineurs during (n = 12; group B) and outside (n = 10; group C) of a migraine without aura attack (total n = 22; group A), including a group of patients tested in both of these phases (n = 5; group D), and compared these results with those obtained from a population of age-comparable, sex- and race-matched healthy volunteers (n = 12; group E). Comparison of the first set of lymphocytes (CD3+CD16 + 56+, CD3-CD16 + 56+, CD3-CD19+, CD3+CD19+, and CD3+HLA - DR+) between the patients in group A and the controls (group E) showed differences, reflecting greater group A percentages of CD3+CD16 + CD56+ and CD3-CD19+ lymphocytes. Furthermore, these differences reached statistical significance only for the CD3+CD16 + CD56+ lymphocytes, and then solely for the patients in group C (Scheffe's test, p < 0.05). Paired analysis of the above lymphocyte markers for subjects in group D failed to show significant differences between patients when they were having and not having a migraine attack, raising the possibility that results from a larger study could show meaningful increases in percentages of CD3+CD16 + CD56+ lymphocytes as one of the immune parameters useful for differentiating migraineurs from controls. Comparison of a second set of lymphocyte markers (CD19+CD5+, CD20+CD72-, CD20-CD72+, CD20+CD72+) among either the different groups of patients or between the patients and controls failed, however, to show statistically significant differences, emphasizing the apparent specificity of the findings described above for CD3+CD16 + CD56+ lymphocytes. Our results, albeit of a preliminary nature, suggest the occurrence of significant, differential changes in lymphocyte subset immunophenotyping between groups of pain-free migraineurs and patients during an acute migraine episode or controls. Corroboration of these findings may prove useful in clinical laboratory practice to identify changes in immunological parameters specifically associated with migraineurs, and help towards a better understanding of the etiology and pathophysiology of this condition.

Decreased Plasma Methionine–Enkephalin Levels in Cluster Headache Patients

“…Besides recognizing that hereditary factors play an important role in the patient's vulnerability to CH, the relatively few genetic studies American Journal of Therapeutics (2012) 19 (3) www.americantherapeutics.com in patients with CH have produced little clinically useful information suggesting, for example, that CH is a channelopathy. 3,[16][17][18] The role of endogenous peptides, including those with opioid-like properties in human health and disease, is amply documented. [12][13][14][15] Although the occurrence of CH seems to be associated with alterations in various immune functions, for example, the expression of natural killer cell activity and generation of lymphokine-activated killer cells, the significance of these preliminary findings is yet unclear.…”

Immunological Aspects in Migraine: Increase of IL‐10 Plasma Levels During Attack

“…Recent studies have attempted to identify specific immune molecules, eg, complement 6 and interleukins 7 as relevant soluble mediators of the immunologic deficit predisposing to migraine 8‐10 …”

“…5 Recent studies have attempted to identify specific immune molecules, eg, complement 6 and interleukins 7 as relevant soluble mediators of the immunologic deficit predisposing to migraine. [8][9][10] In this regard, cytokines such as interleukin(IL)-2, IL-4, IL-6, IL-1, interferon(IFN)-␥ , and granulocytemonocyte colony-stimulating factor (GM-CSF), seem to be involved in the pathogenesis of migraine. 11,12 In our previous study, 13 measurements of plasma IL-4, IL-5, IL-10, and IFN-␥ levels in patients with migraine without aura (MWOA) revealed an increase in IL-5 and IL-4, but not in IFN-␥ or IL-10 during the interictal period.…”

HLA and migraine genes

“…In this light, I would like to stress recent functional studies dealing with lymphocyte trafficking in migraine and immunological mechanisms in pathogenesis of migraine. Emerging results from a sentinel study showed an expansion of normal T cells (CD3+) and of natural killer (NK) cell subsets (CD16+, CD56+) [10,11]. Recent evidence indicates that NK cell activity is directly dependent on L-arginine [12], the main precursor of nitric oxide, and that nitric oxide (NO) in migraine [13] operates synergistically with both the serotonin (5HT) system [14] and the cyclooxygenase (COX) 1 and 2 systems [15] in the development of painful migraine attacks.…”