Therapeutic Effect of IVIG on Inflammatory Arthritis in Mice is Dependent on the Fc Portion and Independent of Sialylation or Basophils

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2014 Apr 25

PMID 24760152

Citations 71

Authors

Ian K Campbell

Sylvia Miescher

Donald R Branch

Patrick J Mott

Alan H Lazarus

Dongji Han

Eugene Maraskovsky

Adrian W Zuercher

Anton Neschadim

Danila Leontyev

Brent S McKenzie

Fabian Kasermann

Affiliations

Soon will be listed here.

Abstract

High-dose i.v. Ig (IVIG) is used to treat various autoimmune and inflammatory diseases; however, the mechanism of action remains unclear. Based on the K/BxN serum transfer arthritis model in mice, IVIG suppression of inflammation has been attributed to a mechanism involving basophils and the binding of highly sialylated IgG Fc to DC-SIGN-expressing myeloid cells. The requirement for sialylation was examined in the collagen Ab-induced arthritis (CAbIA) and K/BxN serum transfer arthritis models in mice. High-dose IVIG (1-2 g/kg body weight) suppressed inflammatory arthritis when given prophylactically. The same doses were also effective in the CAbIA model when given subsequent to disease induction. In this therapeutic CAbIA model, the anti-inflammatory effect of IVIG was dependent on IgG Fc but not F(ab')2 fragments. Removal of sialic acid residues by neuraminidase had no impact on the anti-inflammatory activity of IVIG or Fc fragments. Treatment of mice with basophil-depleting mAbs did not abrogate the suppression of either CAbIA or K/BxN arthritis by IVIG. Our data confirm the therapeutic benefit of IVIG and IgG Fc in Ab-induced arthritis but fail to support the significance of sialylation and basophil involvement in the mechanism of action of IVIG therapy.

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References

Arnson Y, Shoenfeld Y, Amital H . Intravenous immunoglobulin therapy for autoimmune diseases. Autoimmunity. 2009; 42(6):553-60. DOI: 10.1080/08916930902785363. View

Ballow M . The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. J Allergy Clin Immunol. 2010; 127(2):315-23. DOI: 10.1016/j.jaci.2010.10.030. View

Patel D, Puig-Canto A, Challa D, Montoyo H, Ober R, Ward E . Neonatal Fc receptor blockade by Fc engineering ameliorates arthritis in a murine model. J Immunol. 2011; 187(2):1015-22. PMC: 3157913. DOI: 10.4049/jimmunol.1003780. View

Crow A, Suppa S, Chen X, Mott P, Lazarus A . The neonatal Fc receptor (FcRn) is not required for IVIg or anti-CD44 monoclonal antibody-mediated amelioration of murine immune thrombocytopenia. Blood. 2011; 118(24):6403-6. DOI: 10.1182/blood-2011-08-374223. View

Vassilev T, Kazatchkine M, Duong van Huyen J, Mekrache M, Bonnin E, Mani J . Inhibition of cell adhesion by antibodies to Arg-Gly-Asp (RGD) in normal immunoglobulin for therapeutic use (intravenous immunoglobulin, IVIg). Blood. 1999; 93(11):3624-31. View

Leontyev D, Katsman Y, Ma X, Miescher S, Kasermann F, Branch D . Sialylation-independent mechanism involved in the amelioration of murine immune thrombocytopenia using intravenous gammaglobulin. Transfusion. 2012; 52(8):1799-805. DOI: 10.1111/j.1537-2995.2011.03517.x. View

Rossi F, Kazatchkine M . Antiidiotypes against autoantibodies in pooled normal human polyspecific Ig. J Immunol. 1989; 143(12):4104-9. View

Kaveri S, Maddur M, Hegde P, Lacroix-Desmazes S, Bayry J . Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. Clin Exp Immunol. 2011; 164 Suppl 2:2-5. PMC: 3087903. DOI: 10.1111/j.1365-2249.2011.04387.x. View

Ephrem A, Chamat S, Miquel C, Fisson S, Mouthon L, Caligiuri G . Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis. Blood. 2007; 111(2):715-22. DOI: 10.1182/blood-2007-03-079947. View

10.

Bazin R, Lemieux R, Tremblay T . Reversal of immune thrombocytopenia in mice by cross-linking human immunoglobulin G with a high-affinity monoclonal antibody. Br J Haematol. 2006; 135(1):97-100. DOI: 10.1111/j.1365-2141.2006.06245.x. View

11.

Bayry J, Bansal K, Kazatchkine M, Kaveri S . DC-SIGN and alpha2,6-sialylated IgG Fc interaction is dispensable for the anti-inflammatory activity of IVIg on human dendritic cells. Proc Natl Acad Sci U S A. 2009; 106(9):E24. PMC: 2651302. DOI: 10.1073/pnas.0900016106. View

12.

Yu Z, Lennon V . Mechanism of intravenous immune globulin therapy in antibody-mediated autoimmune diseases. N Engl J Med. 1999; 340(3):227-8. DOI: 10.1056/NEJM199901213400311. View

13.

Monach P, Mathis D, Benoist C . The K/BxN arthritis model. Curr Protoc Immunol. 2008; Chapter 15:15.22.1-15.22.12. DOI: 10.1002/0471142735.im1522s81. View

14.

Branch D . Unraveling the IVIG mystique. Transfusion. 2013; 53(2):242-4. DOI: 10.1111/trf.12053. View

15.

Leontyev D, Neschadim A, Branch D . Cytokine profiles in mouse models of experimental immune thrombocytopenia reveal a lack of inflammation and differences in response to intravenous immunoglobulin depending on the mouse strain. Transfusion. 2014; 54(11):2871-9. DOI: 10.1111/trf.12680. View

16.

Nandakumar K, Holmdahl R . Antibody-induced arthritis: disease mechanisms and genes involved at the effector phase of arthritis. Arthritis Res Ther. 2007; 8(6):223. PMC: 1794524. DOI: 10.1186/ar2089. View

17.

Guhr T, Bloem J, Derksen N, Wuhrer M, Koenderman A, Aalberse R . Enrichment of sialylated IgG by lectin fractionation does not enhance the efficacy of immunoglobulin G in a murine model of immune thrombocytopenia. PLoS One. 2011; 6(6):e21246. PMC: 3121734. DOI: 10.1371/journal.pone.0021246. View

18.

Schwab I, Nimmerjahn F . Intravenous immunoglobulin therapy: how does IgG modulate the immune system?. Nat Rev Immunol. 2013; 13(3):176-89. DOI: 10.1038/nri3401. View

19.

Korganow A, Ji H, Mangialaio S, Duchatelle V, Pelanda R, Martin T . From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins. Immunity. 1999; 10(4):451-61. DOI: 10.1016/s1074-7613(00)80045-x. View

20.

McInnes I, Schett G . The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011; 365(23):2205-19. DOI: 10.1056/NEJMra1004965. View