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

Citations Over TimeTop 12% of 2014 papers

Abstract

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 α2,6-sialylated Fc fragments. These reports further suggest that α2,6-sialylated Fc fragments interact with DC-SIGN(+) 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(+) 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.

Related Papers

• → In vitro impact of anti-immunoglobulin E monoclonal antibodies, including omalizumab on whole blood basophil histamine release: Assessment of direct induction of basophil histamine release and evaluation of modulation of allergen-induced basophil histamine release(2017)4 cited
• Measurement of IgE on human basophils: relation to serum IgE and anti-IgE-induced histamine release.(1977)
• → Measurement of IgE on Human Basophils: Relation to Serum IgE and Anti-IgE-Induced Histamine Release(1977)188 cited
• The quantification of IgE antibody specific for ragweed Antigen E (AgE) on the basophil surface in patients with ragweed pollenosis.(1978)
• → Studies on Basophil Reactivity(1985)