Overview of intravenous immune globulin (IVIG) therapy
- Arthur J Silvergleid, MD
Arthur J Silvergleid, MD
- Section Editor — Transfusion Medicine
- Affiliate Associate Professor, Department of Pathology and Cell Biology
- University of South Florida, College of Medicine
- Medical Director, OneBlood, Inc.
- Mark Ballow, MD
Mark Ballow, MD
- Professor of Pediatrics
- All Children’s Hospital
- University of South Florida School of Medicine
- Section Editors
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- E Richard Stiehm, MD
E Richard Stiehm, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Immunology and Immunodeficiency
- Distinguished Research Professor of Pediatrics
- David Geffen School of Medicine at UCLA
Immune globulin derived from the plasma of paid and volunteer donors is used in the treatment of an array of disorders, including primary and secondary immune deficiency states and a variety of autoimmune and inflammatory disorders.
This topic will review the indications, proposed mechanisms of action, and administration of intravenous immune globulin (IVIG).
Additional topic reviews discuss the adverse effects of IVIG therapy and the administration of immune globulin by subcutaneous and intramuscular routes. (See "Intravenous immune globulin: Adverse effects" and "Subcutaneous and intramuscular immune globulin therapy".)
The use of IVIG in the treatment of specific disease states is discussed separately. (See 'Indications' below.)
Several terms are used for immune globulin preparations according to the route of administration:
- Kaveri SV, Dietrich G, Hurez V, Kazatchkine MD. Intravenous immunoglobulins (IVIg) in the treatment of autoimmune diseases. Clin Exp Immunol 1991; 86:192.
- Tankersley DL. Dimer formation in immunoglobulin preparations and speculations on the mechanism of action of intravenous immune globulin in autoimmune diseases. Immunol Rev 1994; 139:159.
- Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med 2012; 367:2015.
- 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 2011; 127:315.
- Ballow M. Mechanisms of immune regulation by IVIG. Curr Opin Allergy Clin Immunol 2014; 14:509.
- Teeling JL, Jansen-Hendriks T, Kuijpers TW, et al. Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia. Blood 2001; 98:1095.
- Samuelsson A, Towers TL, Ravetch JV. Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science 2001; 291:484.
- Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 2011; 475:110.
- Fehr J, Hofmann V, Kappeler U. Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gamma globulin. N Engl J Med 1982; 306:1254.
- Crow AR, Song S, Semple JW, et al. IVIg inhibits reticuloendothelial system function and ameliorates murine passive-immune thrombocytopenia independent of anti-idiotype reactivity. Br J Haematol 2001; 115:679.
- Kaveri SV, Lacroix-Desmazes S, Bayry J. The antiinflammatory IgG. N Engl J Med 2008; 359:307.
- Siedlar M, Strach M, Bukowska-Strakova K, et al. Preparations of intravenous immunoglobulins diminish the number and proinflammatory response of CD14+CD16++ monocytes in common variable immunodeficiency (CVID) patients. Clin Immunol 2011; 139:122.
- Turhan A, Jenab P, Bruhns P, et al. Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes. Blood 2004; 103:2397.
- Viard I, Wehrli P, Bullani R, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 1998; 282:490.
- Kaneko Y, Nimmerjahn F, Ravetch JV. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 2006; 313:670.
- Anthony RM, Wermeling F, Karlsson MC, Ravetch JV. Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci U S A 2008; 105:19571.
- Tackenberg B, Jelcic I, Baerenwaldt A, et al. Impaired inhibitory Fcgamma receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proc Natl Acad Sci U S A 2009; 106:4788.
- McCormick JK, Yarwood JM, Schlievert PM. Toxic shock syndrome and bacterial superantigens: an update. Annu Rev Microbiol 2001; 55:77.
- Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens [see comment]. J Clin Invest 1993; 91:602.
- Norrby-Teglund A, Basma H, Andersson J, et al. Varying titers of neutralizing antibodies to streptococcal superantigens in different preparations of normal polyspecific immunoglobulin G: implications for therapeutic efficacy. Clin Infect Dis 1998; 26:631.
- Ashkenazi S, Cleary TG, Lopez E, Pickering LK. Anticytotoxin-neutralizing antibodies in immune globulin preparations: potential use in hemolytic-uremic syndrome. J Pediatr 1988; 113:1008.
- Palla R, Cirami C, Panichi V, et al. Intravenous immunoglobulin therapy of membranous nephropathy: efficacy and safety. Clin Nephrol 1991; 35:98.
- Spycher M, Matozan K, Minnig K, et al. In vitro comparison of the complement-scavenging capacity of different intravenous immunoglobulin preparations. Vox Sang 2009; 97:348.
- Basta M, Van Goor F, Luccioli S, et al. F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins. Nat Med 2003; 9:431.
- Othy S, Hegde P, Topçu S, et al. Intravenous gammaglobulin inhibits encephalitogenic potential of pathogenic T cells and interferes with their trafficking to the central nervous system, implicating sphingosine-1 phosphate receptor 1-mammalian target of rapamycin axis. J Immunol 2013; 190:4535.
- Trinath J, Hegde P, Sharma M, et al. Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells. Blood 2013; 122:1419.
- Olivito B, Taddio A, Simonini G, et al. Defective FOXP3 expression in patients with acute Kawasaki disease and restoration by intravenous immunoglobulin therapy. Clin Exp Rheumatol 2010; 28:93.
- Tjon AS, Tha-In T, Metselaar HJ, et al. Patients treated with high-dose intravenous immunoglobulin show selective activation of regulatory T cells. Clin Exp Immunol 2013; 173:259.
- Yu Z, Lennon VA. Mechanism of intravenous immune globulin therapy in antibody-mediated autoimmune diseases. N Engl J Med 1999; 340:227.
- Bleeker WK, Teeling JL, Hack CE. Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect. Blood 2001; 98:3136.
- Darabi K, Abdel-Wahab O, Dzik WH. Current usage of intravenous immune globulin and the rationale behind it: the Massachusetts General Hospital data and a review of the literature. Transfusion 2006; 46:741.
- Appropriate uses of human immunoglobulin in clinical practice: memorandum from an IUIS/WHO meeting. Bull World Health Organ 1982; 60:43.
- Requirements for the collection, processing, and quality control of blood, blood components, and plasma derivatives. WHO technical Report Series 1989, No. 786, Annex 4.
- Berger M. A history of immune globulin therapy, from the Harvard crash program to monoclonal antibodies. Curr Allergy Asthma Rep 2002; 2:368.
- BRUTON OC. Agammaglobulinemia. Pediatrics 1952; 9:722.
- Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Transfus Med Rev 2003; 17:241.
- Stiehm ER, Casillas AM, Finkelstein JZ, et al. Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: use of an old method with a new product. J Allergy Clin Immunol 1998; 101:848.
- Ducruet T, Levasseur MC, Des Roches A, et al. Pharmacoeconomic advantages of subcutaneous versus intravenous immunoglobulin treatment in a Canadian pediatric center. J Allergy Clin Immunol 2013; 131:585.
- Gardulf A, Nicolay U, Math D, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol 2004; 114:936.
- Misbah S, Sturzenegger MH, Borte M, et al. Subcutaneous immunoglobulin: opportunities and outlook. Clin Exp Immunol 2009; 158 Suppl 1:51.
- Ahsan N, Wiegand LA, Abendroth CS, Manning EC. Acute renal failure following immunoglobulin therapy. Am J Nephrol 1996; 16:532.
- Chacko B, John GT, Balakrishnan N, et al. Osmotic nephropathy resulting from maltose-based intravenous immunoglobulin therapy. Ren Fail 2006; 28:193.
- Welles CC, Tambra S, Lafayette RA. Hemoglobinuria and acute kidney injury requiring hemodialysis following intravenous immunoglobulin infusion. Am J Kidney Dis 2010; 55:148.
- Kahwaji J, Barker E, Pepkowitz S, et al. Acute hemolysis after high-dose intravenous immunoglobulin therapy in highly HLA sensitized patients. Clin J Am Soc Nephrol 2009; 4:1993.
- Seifner A, Beck G, Bayer P, et al. Assessment of immunoglobulin concentrates on thrombogenic activity by thrombin generation assay, prekallikrein activator assay, and size-exclusion chromatography. Transfusion 2014; 54:376.
- http://www.fda.gov/downloads/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/UCM258022.pdf (Accessed on August 04, 2015).
- Ameratunga R, Sinclair J, Kolbe J. Increased risk of adverse events when changing intravenous immunoglobulin preparations. Clin Exp Immunol 2004; 136:111.
- Lucas M, Lee M, Lortan J, et al. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol 2010; 125:1354.
- Hachulla E. [IgIV at home:experience of a center--economic aspects]. Rev Med Interne 2007; 28 Spec No. 1:7.
- Brennan VM, Salomé-Bentley NJ, Chapel HM, Immunology Nurses Study. Prospective audit of adverse reactions occurring in 459 primary antibody-deficient patients receiving intravenous immunoglobulin. Clin Exp Immunol 2003; 133:247.
- Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Allergy Clin Immunol 2008; 122:210.
- Chapel HM, Lee M. Immunoglobulin replacement in patients with chronic lymphocytic leukemia (CLL): kinetics of immunoglobulin metabolism. J Clin Immunol 1992; 12:17.
- Daw Z, Padmore R, Neurath D, et al. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis. Transfusion 2008; 48:1598.
- MECHANISMS OF ACTION
- Protection against infection
- Suppression of inflammatory/autoimmune processes
- Uses for IVIG
- Uses for hyperimmune globulin
- PRETREATMENT TESTING
- PRODUCTION AND COMPOSITION
- SELECTING A PRODUCT
- Selection of IVIG versus other routes
- Selection among IVIG products
- DOSING AND ADMINISTRATION
- Product handling and storage
- Home versus healthcare facility administration
- Dosing in different disorders
- - Immune deficiencies
- - Inflammatory/autoimmune disorders
- Interval between doses
- Infusion rates
- Dosing in obese patients
- VACCINATION OF PATIENTS RECEIVING IVIG
- CONSENT AND RECORD KEEPING
- ADVERSE EFFECTS
- SUMMARY AND RECOMMENDATIONS