Abstract text (incl. figure legends and references)

Objective: Within the multifactorial etiology of migraine, accumulating evidence suggests a role for the immune system. However, the specific contribution of innate and adaptive immunity to migraine remains unclear. Hence, we investigated the association of innate and adaptive immunity with migraine. Additionally, we explored the role of the balance between the two components in migraine. Methods: We measured white-blood-cell type based immunity markers and calculated their derived ratios using blood samples collected during interictal periods and assessed the prevalence of migraine using a structured interview with participants of the prospective population-based Rotterdam Study. We assessed neutrophil and platelet counts as a proxy for innate and lymphocyte count as a proxy for adaptive immunity. The balance between the two components was assessed by the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII). We investigated associations of blood cell counts, and their derived ratios with migraine using logistic regression models adjusting for age, sex and other variables. Results: Among 6593 participants (mean age 65.6 ± 11.2 years, 56.7 % female), 995 (15.1%) had migraine. We found no association between neutrophil (Odds Ratio [OR] per standard deviation increase 1.02 95% Confidence Interval [CI] 0.94-1.10), platelet (OR 1.01 CI 0.93 – 1.09) or lymphocyte counts (OR 1.01 CI 0.93 – 1.09) and migraine status. Similarly, no associations were observed between NLR (OR 1.01 CI 0.94 – 1.09), PLR (OR 1.00 CI 0.93 – 1.08) and SII (OR 1.01 CI 0.94 – 1.09) and migraine status. In the analyses with migraine subgroups, a significant association was observed between the platelet count and migraine with aura (OR 1.17, CI 1.01 – 1.35). Conclusion: Our results do not support the involvement of innate and adaptive immunity in migraine. Platelet count and migraine with aura relationship needs further investigation.