Intravenous immunoglobulin-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients

Meenu Sharma (1, 2) , Yoland Schoindre (3) , Pushpa Hegde (2) , Chaitrali Saha (2, 1) , Mohan S Maddur (2) , Emmanuel Stephen-Victor (2) , Laurent Gilardin (2) , Maxime Lecerf (2) , Patrick Bruneval (4) , Luc Mouthon (5, 6) , Olivier Benveniste (7, 3) , Srini V Kaveri (8, 2) , Jagadeesh Bayry (2, 8)

1 UTC - Université de Technologie de Compiègne
2 CRC - Centre de Recherche des Cordeliers
3 CHU Pitié-Salpêtrière [AP-HP]
4 Anatomie pathologique [CHU Pompidou]
5 IC UM3 (UMR 8104 / U1016) - Institut Cochin
6 Centre National de Référence pour les Maladies Systémiques Autoimmunes Rares
7 Centre de recherche en myologie
8 ICMR - Indian Council of Medical Research [New Dehli]

Intravenous immunoglobulin (IVIg) is used in the therapy of various autoimmune and inflammatory diseases. Recent studies in experimental models propose that anti-inflammatory effects of IVIg are mainly mediated by a2,6-sialylated Fc fragments. These reports further suggest that a2,6-sialylated Fc fragments interact with DC-SIGN 1 cells to release IL-33 that subsequently expands IL-4-producing basophils. However, translational insights on these observations are lacking. Here we show that IVIg therapy in rheumatic patients leads to significant raise in plasma IL-33. However, IL-33 was not contributed by human DC-SIGN 1 dendritic cells and splenocytes. As IL-33 has been shown to expand basophils, we analyzed the proportion of circulating basophils in these patients following IVIg therapy. In contrast to mice data, IVIg therapy led to basophil expansion only in two patients who also showed increased plasma levels of IL-33. Importantly, the fold-changes in IL-33 and basophils were not correlated and we could hardly detect IL-4 in the plasma following IVIg therapy. Thus, our results indicate that IVIg-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients. Hence, IL-33 and basophil-mediated anti-inflammatory mechanism proposed for IVIg might not be pertinent in humans.

Domaines: Immunothérapie

Meenu Sharma, Yoland Schoindre, Pushpa Hegde, Chaitrali Saha, Mohan S Maddur, et al.. Intravenous immunoglobulin-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients. Scientific Reports, 2014, 4 (1), pp.5672. ⟨10.1038/srep05672⟩. ⟨hal-01358914⟩