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. 2018 Jan;141(1):399-402.e8.
doi: 10.1016/j.jaci.2017.06.021. Epub 2017 Jul 18.

Sialylation of IgG antibodies inhibits IgG-mediated allergic reactions

Alexandra Epp  1 , Juliane Hobusch  1 , Yannic C Bartsch  1 , Janina Petry  1 , Gina-Maria Lilienthal  1 , Carolien A M Koeleman  2 , Simon Eschweiler  1 , Christian Möbs  3 , Ashley Hall  4 , Suzanne C Morris  5 , Dominique Braumann  6 , Christine Engellenner  7 , Josephine Bitterling  1 , Johann Rahmöller  8 , Alexei Leliavski  1 , Robina Thurmann  1 , Mattias Collin  9 , Kelley W Moremen  10 , Richard T Strait  4 , Véronique Blanchard  11 , Arnd Petersen  12 , Timo Gemoll  13 , Jens K Habermann  13 , Frank Petersen  7 , Andreas Nandy  14 , Helga Kahlert  14 , Michael Hertl  3 , Manfred Wuhrer  2 , Wolfgang Pfützner  3 , Uta Jappe  15 , Fred D Finkelman  16 , Marc Ehlers  17
Affiliations

Sialylation of IgG antibodies inhibits IgG-mediated allergic reactions

Alexandra Epp et al. J Allergy Clin Immunol. 2018 Jan.
No abstract available

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Conflict of interest statement

Disclosure of potential conflict of interest:

Hansa Medical AB (HMAB) (www.hansamedical.com) holds patents for using EndoS as a treatment for antibody-mediated diseases. M.C. is listed as one of the inventors on these applications and has a royalty agreement with HMAB. Genovis AB (GAB) (www.genovis.com) holds patents for the biotechnological use of EndoS where M.C. is listed as an inventor. HMAB and GAB were not involved in any way in the design of the study, writing of the manuscript or the decision to publish.

The rest of the authors declare that they have no relevant conflicts of interest and no financial interests.

Figures

FIG 1
FIG 1. Effect of differently glycosylated IgG subclass Abs on IgE- and IgG-mediated murine anaphylaxis
A, The conserved biantennary N-glycan (four N-acetylglucosamines (dark blue) and three mannoses (green)) at Asn 297 in the IgG Fc part can be modified by fucose (red), bisecting GlcNAc (light blue), galactose (G; yellow) and sialic acid (S; magenta). The cleavage site of EndoS used for IgG glycan analysis is depicted. B, Experimental design of IgE-mediated anaphylaxis as done in D and E. C, Fc glycosylation profiles of the differently glycosylated murine IgG1 anti-TNP mAbs (clone H5) that were used in the murine experiments; native=low-galactosylated (low-gal), in vitro galactosylated (gal) or galactosylated plus sialylated (sial). D and E, Inhibition of IgE-mediated temperature drop by differently glycosylated IgG1 anti-TNP mAbs (H5) in (D) wt and (E) FcγRIIb-deficient mice (in each graph: no IgG, n=8–10; low-gal, n=8–10; gal, n=5; sial, n=5); symbols represent means. One of two independent experiments is shown. F, Experimental design of IgG-mediated anaphylaxis as done in G–I. G–I, Decrease in body temperature induced with differently glycosylated IgG subclass anti-TNP mAbs in (G–I) wt or (H) FcγRIIb-deficient mice (G–I) without or (I) with α-SignR1 treatment; de-gal: in vitro de-sialylated plus de-galactosylated. (G) Pooled data (n=10–15) from independent experiments with n=5/group/experiment or (H, I) one of two independent experiments is shown.
FIG 2
FIG 2. Bet v 1-specific serum IgG Fc glycosylation of untreated and treated allergic patients and influence of different adjuvants on IgG Fc glycosylation
A, Serum titers of Bet v 1-specific IgG1 and IgG4 from untreated (season, n=8; no season, n=6 + 11 (AIT-treated, month (m) 0)) and AIT-treated (n=11) birch pollen allergic patients; black line: mean; gray: pollen season. The green data points depict the 5 AIT-treated patients who were selected for the glycan analysis in B and C and Fig E2, while the red data points depict the 3 samples (patient 5 at m12 (5–12) and 5–36 and 21-18) that were chosen for in vitro de-sialylation and neutrophil activation in B–E and Fig E2. One of two independent ELISAs is shown. B and C, Percentage of (B) agalactosylated (G0) and (C) sialylated glycans from purified Bet v 1-specific IgG Abs of untreated (season, n=5; no season, n=5 + 5 (AIT-treated, m0) and the 5 selected AIT-treated patients and from IVIg and purified native and in vitro de-sialylated total serum IgG from patient samples 5–12, 5–36 and 21-18. The filled areas indicate the levels of agalactosylated (G0) or sialylated IgG autoAbs in RA patients for comparisonE14. D and E, Human neutrophil activation assay. (D) Experimental setup and (E) ROS production after activation with native or in vitro de-sialylated Bet v 1-specific IgG Abs of patient 5 (P5 m36); no IgG (black). One of two independent ROS assays is shown. F–J, The effect of distinct adjuvants (eCFA, alum or MPLA) on the induction of OVA-specific serum IgG Abs. F, Experimental design. G, IgG1 and IgG2 (IgG2b+IgG2c; both cannot be distinguished by glycopeptide analysis because of the comparable peptide sequence) frequencies in purified OVA-specific IgG Abs as determined by glycopeptide analysis. H and I, (H) IgG1 and IgG2 or (I) total IgG Fc sialylation profiles of pooled and purified OVA-specific IgG Abs as determined by (H) glycopeptide or (I) total IgG glycan analysis. J, IgG-mediated anaphylaxis as described in Fig 1, F with 100 µg of pooled and purified OVA-specific serum IgG Abs; n=4–5 per group. Symbols represent means.
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