Investigating the modulation of plasma IgA levels and neutrophil activation after stroke

17 million people suffer from stroke every year. Among those, more than 50% of patients exhibit high cholesterol levels at admission, which makes hyperlipidemia one of the most common comorbidities. Furthermore, after stroke, about one third of patients show signs of infection. Yet, there is no targeted therapy for patients with hyperlipidemia, or no targeted therapy against infections and studies investigating these conditions are scarce. Hence, this study focuses on the most abundant mucosal antibody, Immunoglobulin A (IgA) and the effects of hyperlipidemia on immune system regulation after stroke. In this study, it is shown that stroke reduces the numbers of B cells in Peyer’s patches (PP), which might lead to the decreased levels of plasma IgA levels. This condition might make patients susceptible to infections, increasing morbidity and mortality. The negative correlation between neutrophil activation and plasma IgA levels can be a result of activated neutrophils, which causes PP B cell number and plasma IgA decrease, and it is crucial to understand the exact pathophysiological mechanisms and activation patterns of neutrophils. As most of the patients are introduced to stroke unit with comorbidities, the preclinical model of hyperlipidemia is utilized and these mice also show smaller numbers of B cells in PPs and reduced plasma IgA after stroke. These comorbidities might be related to worse outcome via induction of early neutrophil activation and PP B cell decrease. Neutrophils being early activators after stroke, our analysis and experimental paradigm show that the innate immune system is more activated, and more proinflammatory cytokines are released in Western Diet (WD) fed animals within the therapeutic window after stroke, causing significantly more damage in the brain. Preclinical studies focusing on early immune response in animals with comorbidities will be fundamental to find key therapeutic targets in stroke. As a result, targeting early innate immune response should be one of the keys aims in stroke treatment with more emphasis on patients with comorbidities. Mechanistic understanding for IgA regulation and the role of neutrophil extracellular traps (NETs) in this process might open a new path to develop new therapeutic targets.