Intravenous immunoglobulin (IVIG) is a cornerstone of autoimmune disease therapy, but its use is constrained by high costs and limited supply. A sialylated IgG1 Fc variant with enhanced affinity for the inhibitory Fcγ receptor FcγRIIB could offer an effective dose-sparing alternative to IVIG, potentially transforming treatments for autoimmune diseases.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$32.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Bayry, J. et al. Intravenous immunoglobulin: mechanism of action in autoimmune and inflammatory conditions. J. Allergy Clin. Immunol. Pract. 11, 1688–1697 (2023).
Schwab, I. & Nimmerjahn, F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat. Rev. Immunol. 13, 176–189 (2013).
Jones, A. T., Marino, A. E., Martynyuk, T., Bournazos, S. & Ravetch, J. V. The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptors. Science 390, eadv2927 (2025).
Schwab, I. et al. Broad requirement for terminal sialic acid residues and FcγRIIB for the preventive and therapeutic activity of intravenous immunoglobulins in vivo. Eur. J. Immunol. 44, 1444–1453 (2014).
Pincetic, A. et al. Type I and type II Fc receptors regulate innate and adaptive immunity. Nat. Immunol. 15, 707–716 (2014).
Temming, A. R. et al. Human DC-SIGN and CD23 do not interact with human IgG. Sci. Rep. 9, 9995 (2019).
Samuelsson, A., Towers, T. L. & Ravetch, J. V. Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science 291, 484–486 (2001).
Spirig, R. et al. rIgG1 Fc hexamer inhibits antibody-mediated autoimmune disease via effects on complement and FcγRs. J. Immunol. 200, 2542–2553 (2018).
Abdeldaim, D. T. & Schindowski, K. Fc-engineered therapeutic antibodies: recent advances and future directions. Pharmaceutics 15, 2402 (2023).
Rambabu, N. et al. Regulation of immune cell metabolism by therapeutic normal IgG intravenous immunoglobulin. J. Allergy Clin. Immunol. 156, 418–432 (2025).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Retnakumar, S.V., Bayry, J. Engineered sialylated IgG1 Fc as a dose-sparing alternative to IVIG. Nat Rev Rheumatol 22, 149–150 (2026). https://doi.org/10.1038/s41584-025-01347-1
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41584-025-01347-1
