IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators.

Wehrli, Marc; Schneider, Christoph; Cortinas-Elizondo, Fabiola; Verschoor, Daniëlle; Frias Boligan, Kayluz; Adams, Olivia Joan; Hlushchuk, Ruslan; Engelmann, Christine; Daudel, Fritz; Villiger, Peter M.; Seibold, Frank; Yawalkar, Nikhil; Vonarburg, Cédric; Miescher, Sylvia; Lötscher, Marius; Kaufmann, Thomas; Münz, Christian; Mueller, Christoph; Djonov, Valentin; Simon, Hans-Uwe; ... (2020). IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators. Journal of immunology, 205(10), pp. 2640-2648. American Association of Immunologists 10.4049/jimmunol.1900883

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IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK-, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.

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