Precision Medicine as Treatment for Primary Immunodeficiency and Immune Dysregulation
Abstract
“Precision medicine” is the use of therapy that targets the molecular basis of a patient’s disease process. This approach is increasingly well-established in treatment of monogenic disorders of immunity, including primary immunodeficiencies and primary immune regulatory disorders. This is due to the exquisite detail with which many immune pathways have been defined, and the wide variety of immune modulatory medications that target these pathways. Here we review many of the most effective uses of this approach and suggest a framework for classifying these strategies.
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2. Shehata N, Palda V, Bowen T, et al. The Use of Immunoglobulin Therapy for Patients With Primary Immune Deficiency: An Evidence-Based Practice Guideline. Transfus Med Rev 2010;24(SUPPL. 1).
3. 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(3):S1–46.
4. Ballow M. Mechanisms of immune regulation by IVIG. Curr. Opin. Allergy Clin. Immunol. 2014;14(6):509–15.
5. ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-Deaminase Deficinecy in Two Patients With Severely Impaired Cellular Immunity. Lancet 1972;300(7786):1067–9.
6. Zegers BJM, Stoop JW. Metabolic Causes of Immune Deficiency: Mechanisms and Treatment. In: Immunodeficiency and Disease. 1988. p. 113–31.
7. Hershfield MS, Buckley RH, Greenberg ML, et al. Treatment of Adenosine Deaminase Deficiency with Polyethylene Glycol–Modified Adenosine Deaminase. N Engl J Med 1987;316(10):589–96.
8. Hershfield MS. PEG‐ADA: An alternative to haploidentical bone marrow transplantation and an adjunct to gene therapy for adenosine deaminase deficiency. Hum. Mutat. 1995;5(2):107–12.
9. Gaspar HB, Aiuti A, Porta F, Candotti F, Hershfield MS, Notarangelo LD. How I treat ADA deficiency. Blood 2009;114:3524–32.
10. Gaspar HB, Cooray S, Gilmour KC, et al. Immunodeficiency: Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction. Sci Transl Med 2011;3(97).
11. Sharma A, Jacob A, Tandon M, Kumar D. Orphan drug: Development trends and strategies. J Pharm Bioallied Sci 2010;2(4):290.
12. Chambers CA, Krummel ME, Boitel B, et al. The Role of CTLA-4 in the Regulation and Initiation of T-Cell Responses. Immunol Rev 1996;153(1):27–46.
13. Lo B, Zhang K, Lu W, et al. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 2015;349(6246):436–40.
14. Schubert D, Bode C, Kenefeck R, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med 2014;20(12):1410–6.
15. Kuehn O. Immune Dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 2014;4:6–11.
16. Lo B, Fritz JM, Su HC, Uzel G, Jordan MB, Lenardo MJ. CHAI and LATAIE: New genetic diseases of CTLA-4 checkpoint insufficiency. Blood 2016;128(8):1037–42.
17. Alangari A, Alsultan A, Adly N, et al. LPSresponsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol 2012;130(2):481–8.
18. Lopez-Herrera G, Tampella G, PanHammarström Q, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet 2012;90:986–1001.
19. Kiykim A, Ogulur I, Dursun E, et al. Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency. J Allergy Clin Immunol Pract 2019; 20. Schwab C, Gabrysch A, Olbrich P, et al.Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4–insufficient subjects. J Allergy Clin Immunol 2018;142(6):1932–46.
21. Baehner RL, Nathan DG. Leukocyte oxidase: Defective activity in chronic granulomatous disease. Science 1967;155(3764):835–6.
22. Quie PG, White JG, Holmes B, Good RA. In vitro bactericidal capacity of human polymorphonuclear leukocytes: diminished activity in chronic granulomatous disease of childhood. J Clin Invest 1967;46(4):668–79.
23. Holland SM. Chronic Granulomatous Disease. Hematol Oncol Clin North Am 2013;27(1):89–99.
24. Thomsen IP, Smith MA, Holland SM, Creech CB. A Comprehensive Approach to the Management of Children and Adults with Chronic Granulomatous Disease. J Allergy Clin Immunol Pract 2016;4(6):1082–8.
25. Kuhns DB, Alvord WG, Heller T, et al. Residual NADPH Oxidase and Survival in Chronic Granulomatous Disease. N Engl J Med 2010;363(27):2600–10.
26. Marciano BE, Spalding C, Fitzgerald A, et al. Common Severe Infections in Chronic Granulomatous Disease. Clin Infect Dis 2015;60(8):1176–83.
27. Slack MA, Thomsen IP. Prevention of Infectious Complications in Patients With Chronic Granulomatous Disease. J Pediatric Infect Dis Soc 2018;7(suppl1):S25-S30.
28. Ezekowitz RA, Orkin SH, Newburger PE. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous disease gene expression in Xlinked variant chronic granulomatous disease. J Clin Invest 1987;80(4):1009–16.
29. International Chronic Granulomatous Disease Cooperative Study Group. A Controlled Trial of Interferon Gamma to Prevent Infection in Chronic Granulomatous Disease. N Engl J Med 1991;324(8):509–16.
30. Marciano BE, Wesley R, De Carlo ES, et al. Long-Term Interferon-Therapy for Patients with Chronic Granulomatous Disease. Clin Infect Dis 2004;39(5):692–9.
31. Jackson SH, Miller GF, Segal BH, et al. IFN- $γ$ Is Effective in Reducing Infections in theMouse Model of Chronic Granulomatous Disease (CGD). J Interf Cytokine Res 2001;21(8):567–73.
32. Naderi beni F, Fattahi F, Mirshafiey A, et al. Increased production of nitric oxide by neutrophils from patients with chronic granulomatous disease on interferon-gamma treatment. Int Immunopharmacol 2012;12(4):689–93.
33. Bustamante J, Boisson-Dupuis S, Abel L, Casanova J-L. Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity. Semin Immunol 2014;26(6):454–70.
34. Rosain J, Kong X, Martinez‐Barricarte R, et al. Mendelian susceptibility to mycobacterial disease: 2014–2018 update. Immunol & Cell Biol 2019;97(4):360–7.
35. Kotenko S V., Izotova LS, Pollack BP, et al. Interaction between the Components of the Interferon γ Receptor Complex. J Biol Chem 1995;270(36):20915–21.36. Jouanguy E, Lamhamedi-Cherradi S, Altare F, et al. Partial interferon-gamma receptor 1 deficiency in a child with tuberculoid bacillus Calmette-Guérin infection and a sibling with clinical tuberculosis. J Clin Invest 1997;100(11):2658–64.
37. Remiszewski P, Roszkowska-Śliz B, Winek J, et al. Disseminated Mycobacterium avium Infection in a 20-Year-Old Female with Partial Recessive IFNγR1 Deficiency. Respiration 2006;73(3):375–8.
38. Ward CM, Jyonouchi H, Kotenko S V, et al. Adjunctive treatment of disseminated Mycobacterium avium complex infection with interferon alpha-2b in a patient with complete interferon-gamma receptor R1 deficiency. Eur J Pediatr 2007;166(9):981–5.
39. Liu S-Y, Sanchez DJ, Aliyari R, Lu S, Cheng G. Systematic identification of type I and type II interferon-induced antiviral factors. Proc Natl Acad Sci 2012;109(11):4239–44.
40. Bax HI, Freeman AF, Ding L, et al. Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling. J Clin Immunol 2013;33(5):991–1001.
41. Bouchonnet F, Boechat N, Bonay M, Hance AJ. Alpha/beta interferon impairs the ability of human macrophages to control growth of Mycobacterium bovis BCG. Infect Immun 2002;70(6):3020–5.
42. Nguyen KB, Cousens LP, Doughty LA, Pien GC, Durbin JE, Biron CA. Interferon α/βmediated inhibition and promotion of interferon γ: STAT1 resolves a paradox. Nat Immunol 2000;1(1):70–6.
43. de Wetering D van, van Wengen A, Savage NDL, van de Vosse E, van Dissel JT. IFN-α cannot substitute lack of IFN-γ responsiveness in cells of an IFN-γR1 deficient patient. Clin Immunol 2011;138(3):282–90.
44. Alangari AA, Al-Zamil F, Al-Mazrou A, et al. Treatment of disseminated mycobacterial infection with high-dose IFN-γ in a patient with IL-12Rβ1 deficiency. Clin Dev Immunol 2011;2011:691956.
45. Prando C, Samarina A, Bustamante J, et al. Inherited IL-12p40 Deficiency. Medicine (Baltimore) 2013;92(2):109–22.
46. Villarino A V., Kanno Y, O’Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat. Immunol. 2017;18(4):374–84.
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| Files | ||
| Issue | Vol 2, No 4 (2019) | |
| Section | Review Article | |
| DOI | https://doi.org/10.22034/igj.2019.206436.1026 | |
| Keywords | ||
| precision medicine targeted therapy primary immunodeficiency disease immune dysregulation | ||
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How to Cite
1.
Hoyos-Bachiloglu R, Platt C. Precision Medicine as Treatment for Primary Immunodeficiency and Immune Dysregulation. Immunol Genet J. 2019;2(4):153-172.
