Evidence map›Paper›PMID 26436649›Full record

Trial reportThe Journal of clinical investigation2015

Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity.

Isaak Quast, Christian W Keller, Michael A Maurer, John P Giddens, Björn Tackenberg, Lai-Xi Wang, Christian Münz, Falk Nimmerjahn, Marinos C Dalakas, Jan D Lünemann

Registry-linked trialOpen access · bronzeAbstract readComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03394092 (Changes in Glycopeptides of Serum Immunoglobulin G in Patients With Acute Myocardial Infarction and the Relationships Between Its Change and Prognosis), which is not on this map. Cited by 161 papers.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed
19.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03394092 completednot on this mapstarted 2018, after this paper: background citation

Changes in Glycopeptides of Serum Immunoglobulin G in Patients With Acute Myocardial Infarction and the Relationships Between Its Change and Prognosis

TypeobservationalSponsorThe First Affiliated Hospital of Dalian Medical UniversityRan2018 to 2019Enrolled100ConditionsAcute Coronary SyndromeArmsQuantitative measurements the changes of IgG glycosylation
3 · Its place in the literature

Who cites it

161 citing papers in PubMed, 261 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026
    Article
  8. Review
  9. Not all antibodies are created equal: total IgG glycosylation and severity of antibody-mediated rejection in kidney transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2026
    Article
  10. Review
  11. Antibody glycosylation in neuroimmune diseases.Journal of translational medicine · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Molecular determinants of sialylated IgG anti-inflammatory activity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article

101 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 3 countries.

Isaak Quast
Christian W Keller
Michael A Maurer
John P Giddens
Björn Tackenberg
Lai-Xi Wang
Christian Münz
Falk Nimmerjahn
Marinos C Dalakas
Jan D Lünemann
University of Zurich · CHUniversity of Maryland, College Park · USFriedrich-Alexander-Universität Erlangen-Nürnberg · DEPhilipps University of Marburg · DEThomas Jefferson University · USUniversity of Basel · CH

Funding

EXPAND PARTICIPATION BY MINORITIES IN BIOMEDICAL SCIENCER25GM055036 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI SUMMERS, MICHAEL FINLEY · 1996 to 2021
$16.9M
Synthesis and Function of Antibody Fc Domain GlycoformsR01GM096973 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI WANG, LAI-XI · 2011 to 2020
$2.4M
NIGMS NIH HHS R01 GM096973NIGMS NIH HHS R25 GM055036
6 · The paper itself

Abstract

IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG Fc domains have antiinflammatory properties that are attributed to their ability to increase the activation threshold of innate effector cells to immune complexes by stimulating the upregulation of the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating Fcγ receptors. In contrast, the presence of sialic acid abrogated the increased binding of C1q to Fc-galactosylated IgG1 and resulted in decreased levels of C3b deposition on the cell surface. Similar to monoclonal antibodies, sialic acid inhibited the increased C1q binding to galactosylated Fc fragments in human polyclonal IgG. In sera derived from patients with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system in which humoral immune responses mediate tissue damage, induction of IgG Fc sialylation was associated with clinical disease remission. Thus, impairment of CDC represents an FcγR-independent mechanism by which Fc-sialylated glycovariants might limit proinflammatory IgG effector functions.

Indexed as

Complement Pathway, ClassicalAnimalsAntibody-Dependent Cell CytotoxicityAntigens, CD20B-LymphocytesBurkitt LymphomaCell Line, TumorComplement C1qComplement System ProteinsCytotoxicity, ImmunologicGlycosylationHumansImmunoglobulin GImmunoglobulin gamma-ChainsImmunoglobulins, IntravenousKiller Cells, NaturalAntigens, CD20Complement C1qComplement System ProteinsImmunoglobulin GImmunoglobulin gamma-ChainsImmunoglobulins, IntravenousMyelin-Oligodendrocyte GlycoproteinN-Acetylneuraminic AcidReceptors, IgGRituximab

Identifiers

PMID26436649
PMCPMC4639970
OpenAlexW1874142858

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.