Antibody Diversity in IVIG: Therapeutic Opportunities for Novel Immunotherapeutic Drugs

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Apr 17

PMID 37063852

Authors

Stephan von Gunten

Christoph Schneider

Lejla Imamovic

Guy Gorochov

Affiliations

Soon will be listed here.

Abstract

Significant progress has been made in the elucidation of human antibody repertoires. Furthermore, non-canonical functions of antibodies have been identified that reach beyond classical functions linked to protection from pathogens. Polyclonal immunoglobulin preparations such as IVIG and SCIG represent the IgG repertoire of the donor population and will likely remain the cornerstone of antibody replacement therapy in immunodeficiencies. However, novel evidence suggests that pooled IgA might promote orthobiotic microbial colonization in gut dysbiosis linked to mucosal IgA immunodeficiency. Plasma-derived polyclonal IgG and IgA exhibit immunoregulatory effects by a diversity of different mechanisms, which have inspired the development of novel drugs. Here we highlight recent insights into IgG and IgA repertoires and discuss potential implications for polyclonal immunoglobulin therapy and inspired drugs.

Citing Articles

Attenuation of neutrophil adhesion and formation of neutrophil extracellular traps by pooled human immune globulins.

Rao V, Iqbal S, Young B, Mun C, Jain S, Kaja S Front Pharmacol. 2024; 15:1465776.

PMID: 39734403 PMC: 11672200. DOI: 10.3389/fphar.2024.1465776.

Safety and tolerability of pooled human immune globulins after topical ophthalmic administration in New Zealand White rabbits.

Kaja S, Iqbal S, Pons Lopez B, Molina Zaragoza S, Mun C, Flavin M Cutan Ocul Toxicol. 2024; 43(3):227-231.

PMID: 39086095 PMC: 11383756. DOI: 10.1080/15569527.2024.2381207.

Efficacy of IVIG therapy for patients with sepsis: a systematic review and meta-analysis.

Pan B, Sun P, Pei R, Lin F, Cao H J Transl Med. 2023; 21(1):765.

PMID: 37898763 PMC: 10612304. DOI: 10.1186/s12967-023-04592-8.

References

Resnick E, Moshier E, Godbold J, Cunningham-Rundles C . Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2011; 119(7):1650-7. PMC: 3286343. DOI: 10.1182/blood-2011-09-377945. View

Prasad N, Papoff G, Zeuner A, Bonnin E, Kazatchkine M, Ruberti G . Therapeutic preparations of normal polyspecific IgG (IVIg) induce apoptosis in human lymphocytes and monocytes: a novel mechanism of action of IVIg involving the Fas apoptotic pathway. J Immunol. 1998; 161(7):3781-90. View

von Gunten S, Simon H . Granulocyte death regulation by naturally occurring autoantibodies. Adv Exp Med Biol. 2012; 750:157-72. DOI: 10.1007/978-1-4614-3461-0_12. View

Mahendra A, Sharma M, Rao D, Peyron I, Planchais C, Dimitrov J . Antibody-mediated catalysis: induction and therapeutic relevance. Autoimmun Rev. 2012; 12(6):648-52. DOI: 10.1016/j.autrev.2012.10.009. View

Forbes S, Eschmann M, Mantis N . Inhibition of Salmonella enterica serovar typhimurium motility and entry into epithelial cells by a protective antilipopolysaccharide monoclonal immunoglobulin A antibody. Infect Immun. 2008; 76(9):4137-44. PMC: 2519396. DOI: 10.1128/IAI.00416-08. View

Macpherson A, Yilmaz B, Limenitakis J, Ganal-Vonarburg S . IgA Function in Relation to the Intestinal Microbiota. Annu Rev Immunol. 2018; 36:359-381. DOI: 10.1146/annurev-immunol-042617-053238. View

von Gunten S, Vogel M, Schaub A, Stadler B, Miescher S, Crocker P . Intravenous immunoglobulin preparations contain anti-Siglec-8 autoantibodies. J Allergy Clin Immunol. 2007; 119(4):1005-11. DOI: 10.1016/j.jaci.2007.01.023. View

Mori I, Parizot C, Dorgham K, Demeret S, Amoura Z, Bolgert F . Prominent plasmacytosis following intravenous immunoglobulin correlates with clinical improvement in Guillain-Barré syndrome. PLoS One. 2008; 3(5):e2109. PMC: 2362102. DOI: 10.1371/journal.pone.0002109. View

Harriman G, Bogue M, Rogers P, Finegold M, Pacheco S, Bradley A . Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes. J Immunol. 1999; 162(5):2521-9. View

10.

Sterlin D, Fadlallah J, Adams O, Fieschi C, Parizot C, Dorgham K . Human IgA binds a diverse array of commensal bacteria. J Exp Med. 2020; 217(3). PMC: 7062531. DOI: 10.1084/jem.20181635. View

11.

Cohen I, Efroni S . The Immune System Computes the State of the Body: Crowd Wisdom, Machine Learning, and Immune Cell Reference Repertoires Help Manage Inflammation. Front Immunol. 2019; 10:10. PMC: 6349705. DOI: 10.3389/fimmu.2019.00010. View

12.

Altznauer F, von Gunten S, Spath P, Simon H . Concurrent presence of agonistic and antagonistic anti-CD95 autoantibodies in intravenous Ig preparations. J Allergy Clin Immunol. 2003; 112(6):1185-90. DOI: 10.1016/j.jaci.2003.09.045. View

13.

von Gunten S, Wehrli M, Simon H . Cell death in immune thrombocytopenia: novel insights and perspectives. Semin Hematol. 2013; 50 Suppl 1:S109-15. DOI: 10.1053/j.seminhematol.2013.03.016. View

14.

Fadlallah J, Sterlin D, Fieschi C, Parizot C, Dorgham K, El Kafsi H . Synergistic convergence of microbiota-specific systemic IgG and secretory IgA. J Allergy Clin Immunol. 2018; 143(4):1575-1585.e4. DOI: 10.1016/j.jaci.2018.09.036. View

15.

von Achenbach C, Hevia Hernandez G, von Gunten S . The Choice between Intravenous and Subcutaneous Immunoglobulins: Aspects for Consideration. Pharmacology. 2022; 107(11-12):556-563. DOI: 10.1159/000527655. View

16.

Graeter S, Simon H, von Gunten S . Granulocyte death mediated by specific antibodies in intravenous immunoglobulin (IVIG). Pharmacol Res. 2019; 154:104168. DOI: 10.1016/j.phrs.2019.02.007. View

17.

Maxson R, Jackson R, Smith S . The protective role of enteral IgA supplementation in neonatal gut origin sepsis. J Pediatr Surg. 1995; 30(2):231-3; discussion 233-4. DOI: 10.1016/0022-3468(95)90566-9. View

18.

Langereis J, van der Flier M, de Jonge M . Limited Innovations After More Than 65 Years of Immunoglobulin Replacement Therapy: Potential of IgA- and IgM-Enriched Formulations to Prevent Bacterial Respiratory Tract Infections. Front Immunol. 2018; 9:1925. PMC: 6115500. DOI: 10.3389/fimmu.2018.01925. View

19.

Hiernaux J, Jones J, Rudbach J, Rollwagen F, Baker P . Antibody response of immunodeficient (xid) CBA/N mice to Escherichia coli 0113 lipopolysaccharide, a thymus-independent antigen. J Exp Med. 1983; 157(4):1197-207. PMC: 2186980. DOI: 10.1084/jem.157.4.1197. View

20.

von Gunten S, Smith D, Cummings R, Riedel S, Miescher S, Schaub A . Intravenous immunoglobulin contains a broad repertoire of anticarbohydrate antibodies that is not restricted to the IgG2 subclass. J Allergy Clin Immunol. 2009; 123(6):1268-76.e15. PMC: 2777748. DOI: 10.1016/j.jaci.2009.03.013. View