Intravenous Immunoglobulin (IVIG)
Özet
Intravenous immunoglobulin (IVIG) is a concentrate of immunoglobulins (Ig) prepared from more than 1000 healthy donor sera and contains more than 90% IgG, although there are differences depending on the manufacturer. Although the mechanism of action of IVIG is not clearly known, it is thought to act through multiple mechanisms given its multiple anti-inflammatory effects. IVIG therapy is frequently used off-label in rheumatology and cardiology. It has been approved by the FDA (U.S. Food and Drug Administration) for a number of conditions, including primary immunodeficiency, hypogammaglobulinemia, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and thrombocytopenia in patients with idiopathic thrombocytopenic purpura. IVIG therapy is generally considered a safe treatment, although serious side effects such as thromboembolic events may occasionally occur. Current studies have demonstrated the efficacy of IVIG therapy in the treatment of Kawasaki disease and pericarditis and it is currently recommended in cardiology guidelines. Data on the use of IVIG in myocarditis, dilated cardiomyopathy, peripartum cardiomyopathy, heart failure, atherosclerosis and cardiac transplantation remain limited and further research in this area is emphasised. In acute rheumatic fever, available data suggest that IVIG treatment is ineffective.
İntravenöz immünoglobulin (İVİG), 1000’den fazla sağlıklı donör serumundan hazırlanan immünoglobulinlerin (Ig) bir konsantresi olup üretici firmaya bağlı olarak farklılıklar olmakla birlikte %90’dan fazla IgG içermektedir. Etki mekanizması net olarak bilinmemekle birlikte, çoklu anti-enflamatuar etkileri göz önüne alındığında birden fazla mekanizma yoluyla etki ettiği düşünülmektedir. IVIG tedavisi romatoloji ve kardiyolojide sıklıkla endikasyon dışı olarak kullanılmaktadır. FDA (Amerikan Gıda ve İlaç Dairesi) tarafından primer immün yetmezlik, hipogamaglobulinemi, kronik inflamatuvar demiyelinizan polinöropati, multifokal motor nöropati ve idiyopatik trombositopenik purpura hastalarında trombositopeni gibi çeşitli durumlar için onaylanmıştır. Yaygın olarak güvenli bir tedavi yöntemi olarak kabul edilmektedir; ancak zaman zaman tromboembolik olaylar da dahil olmak üzere ciddi yan etkilere neden olabilmektedir. Mevcut çalışmalar Kawasaki hastalığı ve perikardit tedavisinde İVİG tedavisinin etkinliğini göstermiştir ve şu anda kardiyoloji kılavuzlarında önerilmektedir. Miyokardit, dilate kardiyomiyopati, peripartum kardiyomiyopati, kalp yetmezliği, ateroskleroz ve kardiyak transplantasyonda İVİG kullanımına ilişkin veriler sınırlı kalmakta ve bu alanda daha fazla araştırma yapılması gerektiği vurgulanmaktadır. Akut romatizmal ateşte ise mevcut veriler IVIG tedavisinin etkisiz olduğunu göstermektedir.
Referanslar
Arumugham VB, Rayi A. Intravenous Immunoglobulin (IVIG). In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 4, 2022.
Bayry J, Misra N, Latry V, et al. Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases. Transfus Clin Biol. 2003;10(3):165-169. doi:10.1016/s1246-7820(03)00035-1
Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1-S46. doi:10.1016/j.jaci.2016.09.023
Looney RJ, Huggins J. Use of intravenous immunoglobulin G (IVIG). Best Pract Res Clin Haematol. 2006;19(1):3-25. doi: 10.1016/j.beha.2005.01.032.
Burns JC, Glodé MP. Kawasaki syndrome. Lancet. 2004;364(9433):533-544. doi:10.1016/S0140-6736(04)16814-1
McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association [published correction appears in Circulation. 2019 Jul 30;140(5):e181-e184]. Circulation. 2017;135(17):e927-e999. doi:10.1161/CIR.0000000000000484
Kobayashi T, Saji T, Otani T, et al. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet. 2012;379(9826):1613-1620. doi:10.1016/S0140-6736(11)61930-2
Uehara R, Belay ED, Maddox RA, et al. Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan. Pediatr Infect Dis J. 2008;27(2):155-160. doi:10.1097/INF.0b013e31815922b5
Li X, Chen Y, Tang Y, et al. Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases. Eur J Pediatr. 2018;177(8):1279-1292. doi:10.1007/s00431-018-3182-2
Chbeir D, Gaschignard J, Bonnefoy R, et al. Kawasaki disease: abnormal initial echocardiogram is associated with resistance to IV Ig and development of coronary artery lesions. Pediatr Rheumatol Online J. 2018;16(1):48. Published 2018 Jul 18. doi:10.1186/s12969-018-0264-7
Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991;324(23):1633-1639. doi:10.1056/NEJM199106063242305
Broderick C, Kobayashi S, Suto M, et al. Intravenous immunoglobulin for the treatment of Kawasaki disease. Cochrane Database Syst Rev. 2023;1(1):CD014884. Published 2023 Jan 25. doi:10.1002/14651858.CD014884.pub2
Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110(17):2747-2771. doi:10.1161/01.CIR.0000145143.19711.78
Muta H, Ishii M, Yashiro M, et al. Late intravenous immunoglobulin treatment in patients with Kawasaki disease. Pediatrics. 2012;129(2):e291-e297. doi:10.1542/peds.2011-1704
Muta H, Ishii M, Egami K, et al. Early intravenous gamma-globulin treatment for Kawasaki disease: the nationwide surveys in Japan. J Pediatr. 2004;144(4):496-499. doi:10.1016/j.jpeds.2003.12.033
Imazio M, Battaglia A, Gaido L, et al. Recurrent pericarditis. Rev Med Interne. 2017;38(5):307-311. doi:10.1016/j.revmed.2016.12.006
Moretti M, Buiatti A, Merlo M, et al. Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis. Am J Cardiol. 2013;112(9):1493-1498. doi:10.1016/j.amjcard.2013.06.036
Peterlana D, Puccetti A, Simeoni S, et al. Efficacy of intravenous immunoglobulin in chronic idiopathic pericarditis: report of four cases. Clin Rheumatol. 2005;24(1):18-21. doi:10.1007/s10067-004-0959-7
Tona F, Bellotto F, Laveder F, et al. Efficacy of high-dose intravenous immunoglobulins in two patients with idiopathic recurrent pericarditis refractory to previous immunosuppressive treatment. Ital Heart J. 2003;4(1):64-68.
Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015;36(42):2921-2964. doi:10.1093/eurheartj/ehv318
Schwartz BH, Stein NR, Eshaghian S, et al. Recurrent Myocarditis Treated with Intravenous Immune Globulin and Steroids. Am J Case Rep. 2022;23:e935974. Published 2022 Jul 8. doi:10.12659/AJCR.935974
Robinson JL, Hartling L, Crumley E, et al. A systematic review of intravenous gamma globulin for therapy of acute myocarditis. BMC Cardiovasc Disord. 2005;5(1):12. Published 2005 Jun 2. doi:10.1186/1471-2261-5-12
Kishimoto C, Shioji K, Hashimoto T, et al. Therapy with immunoglobulin in patients with acute myocarditis and cardiomyopathy: analysis of leukocyte balance. Heart Vessels. 2014;29(3):336-342. doi:10.1007/s00380-013-0368-4
Huang X, Sun Y, Su G, et al. Intravenous Immunoglobulin Therapy for Acute Myocarditis in Children and Adults. Int Heart J. 2019;60(2):359-365. doi:10.1536/ihj.18-299
Sherer Y, Levy Y, Shoenfeld Y. Marked improvement of severe cardiac dysfunction after one course of intravenous immunoglobulin in a patient with systemic lupus erythematosus. Clin Rheumatol. 1999;18(3):238-240. doi:10.1007/s100670050091
Gullestad L, Aass H, Fjeld JG, et al. Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation. 2001;103(2):220-225. doi:10.1161/01.cir.103.2.220
Pecoraro A, Crescenzi L, Carucci L, et al. Heart failure not responsive to standard immunosuppressive therapy is successfully treated with high dose intravenous immunoglobulin therapy in a patient with Eosinophilic Granulomatosis with Polyangiitis (EGPA). Int Immunopharmacol. 2017;45:13-15. doi:10.1016/j.intimp.2017.01.025
Kobayashi D, Wada Y, Takata T, et al. A severe form of Churg-Strauss syndrome complicated with acute cardiac failure and rapidly progressive peripheral neuropathy--a possible effect of intravenous immunoglobulin therapy. Intern Med. 2011;50(8):925-929. doi:10.2169/internalmedicine.50.4648
Tsurikisawa N, Taniguchi M, Saito H, et al. Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin. Ann Allergy Asthma Immunol. 2004;92(1):80-87. doi:10.1016/S1081-1206(10)61714-0
Gullestad L, Orn S, Dickstein K, et al. Intravenous immunoglobulin does not reduce left ventricular remodeling in patients with myocardial dysfunction during hospitalization after acute myocardial infarction. Int J Cardiol. 2013;168(1):212-218. doi:10.1016/j.ijcard.2012.09.092
Honigberg MC, Givertz MM. Peripartum cardiomyopathy. BMJ. 2019;364:k5287. Published 2019 Jan 30. doi:10.1136/bmj.k5287
Bozkurt B, Villaneuva FS, Holubkov R, et al. Intravenous immune globulin in the therapy of peripartum cardiomyopathy. J Am Coll Cardiol. 1999;34(1):177-180. doi:10.1016/s0735-1097(99)00161-8
Harding D, Chong MHA, Lahoti N, et al. Dilated cardiomyopathy and chronic cardiac inflammation: Pathogenesis, diagnosis and therapy. J Intern Med. 2023;293(1):23-47. doi:10.1111/joim.13556
Nussinovitch U, Shoenfeld Y. Intravenous immunoglobulin - indications and mechanisms in cardiovascular diseases [published correction appears in Autoimmun Rev. 2011 Jan;10(3):180. Udi, Nussinovitch [corrected to Nussinovitch, Udi]; Yehuda, Shoenfeld [corrected to Shoenfeld, Yehuda]]. Autoimmun Rev. 2008;7(6):445-452. doi:10.1016/j.autrev.2008.04.001
Hazebroek MR, Henkens MTHM, Raafs AG, et al. Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial. Eur J Heart Fail. 2021;23(2):302-309. doi:10.1002/ejhf.2082
McNamara DM, Rosenblum WD, Janosko KM, et al. Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy. Circulation. 1997;95(11):2476-2478. doi:10.1161/01.cir.95.11.2476
McNamara DM, Holubkov R, Starling RC, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation. 2001;103(18):2254-2259. doi:10.1161/01.cir.103.18.2254
Meridor K, Shoenfeld Y, Tayer-Shifman O, et al. Lupus acute cardiomyopathy is highly responsive to intravenous immunoglobulin treatment: Case series and literature review. Medicine (Baltimore). 2021;100(18):e25591. doi:10.1097/MD.0000000000025591
Voss LM, Wilson NJ, Neutze JM, et al. Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial. Circulation. 2001;103(3):401-406. doi:10.1161/01.cir.103.3.401
Cilliers A, Adler AJ, Saloojee H. Anti-inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev. 2015;(5):CD003176. Published 2015 May 28. doi:10.1002/14651858.CD003176.pub3
Aghamajidi A, Gorgani M, Shahba F, et al. The potential targets in immunotherapy of atherosclerosis. Int Rev Immunol. 2023;42(3):199-216. doi:10.1080/08830185.2021.1988591
Nicoletti A, Kaveri S, Caligiuri G, et al. Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice. J Clin Invest. 1998;102(5):910-918. doi:10.1172/JCI119892
Okabe TA, Kishimoto C, Shimada K, et al. Effects of late administration of immunoglobulin on experimental atherosclerosis in apolipoprotein E-deficient mice. Circ J. 2005;69(12):1543-1546. doi:10.1253/circj.69.1543
Keren G, Keren P, Barshack I, et al. The effect of intravenous immunoglobulins on intimal thickening in a mouse model of arterial injury. Atherosclerosis. 2001;159(1):77-83. doi:10.1016/s0021-9150(01)00491-9
Matsuura E, Kobayashi K, Inoue K, et al. Intravenous immunoglobulin and atherosclerosis. Clin Rev Allergy Immunol. 2005;29(3):311-319. doi:10.1385/CRIAI:29:3:311
Wu R, Shoenfeld Y, Sherer Y, et al. Anti-idiotypes to oxidized LDL antibodies in intravenous immunoglobulin preparations--possible immunomodulation of atherosclerosis. Autoimmunity. 2003;36(2):91-97. doi:10.1080/0891693031000080228
Napoli R, Ruvolo A, Triggianese P, et al. Immunoglobulins G modulate endothelial function and affect insulin sensitivity in humans. Nutr Metab Cardiovasc Dis. 2020;30(11):2085-2092. doi:10.1016/j.numecd.2020.07.001
Bourassa-Blanchette S, Patel V, Knoll GA, et al. Clinical outcomes of polyvalent immunoglobulin use in solid organ transplant recipients: A systematic review and meta-analysis - Part II: Non-kidney transplant. Clin Transplant. 2019;33(7):e13625. doi:10.1111/ctr.13625
John R, Lietz K, Burke E, et al. Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients. Circulation. 1999;100(19 Suppl):II229-II235. doi:10.1161/01.cir.100.suppl_2.ii-229
Sarmiento E, Diez P, Arraya M, et al. Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial. Transpl Infect Dis. 2016;18(6):832-843. doi:10.1111/tid.12610
Carbone J, Sarmiento E, Palomo J, et al. The potential impact of substitutive therapy with intravenous immunoglobulin on the outcome of heart transplant recipients with infections. Transplant Proc. 2007;39(7):2385-2388. doi:10.1016/j.transproceed.2007.06.050
Carbone J, Sarmiento E, Del Pozo N, et al. Restoration of humoral immunity after intravenous immunoglobulin replacement therapy in heart recipients with post-transplant antibody deficiency and severe infections. Clin Transplant. 2012;26(3):E277-E283. doi:10.1111/j.1399-0012.2012.01653.x
Stiehm ER. Adverse effects of human immunoglobulin therapy. Transfus Med Rev. 2013;27(3):171-178. doi:10.1016/j.tmrv.2013.05.004
Guo Y, Tian X, Wang X, et al. Adverse Effects of Immunoglobulin Therapy. Front Immunol. 2018;9:1299. Published 2018 Jun 8. doi:10.3389/fimmu.2018.01299
Struff WG, Klasser M, Eckert V, et al. Safety monitoring of a polyvalent immunoglobulin preparation: documentation of 15,548 administrations. Int J Clin Pharmacol Ther. 2005;43(9):420-428. doi:10.5414/cpp43420
Singh-Grewal D, Kemp A, Wong M. A prospective study of the immediate and delayed adverse events following intravenous immunoglobulin infusions. Arch Dis Child. 2006;91(8):651-654. doi:10.1136/adc.2005.078733
Ammann EM, Haskins CB, Fillman KM, et al. Intravenous immune globulin and thromboembolic adverse events: A systematic review and meta-analysis of RCTs. Am J Hematol. 2016;91(6):594-605. doi:10.1002/ajh.24358
Caress JB, Hobson-Webb L, Passmore LV, et al. Case-control study of thromboembolic events associated with IV immunoglobulin. J Neurol. 2009;256(3):339-342. doi:10.1007/s00415-009-0969-0
