Biological Therapies in Patients with Primary Immunodeficiency Diseases

immunoloji-17-1-2024

Tuğba ÖNALANa , Şevket ARSLANa
aNecmettin Erbakan University Faculty of Medicine, Department of Internal Medicine, Division of Immunology and Allergy Diseases, Konya, Türkiye

Önalan T, Arslan Ş. Biological therapies in patients with primary immunodeficiency diseases. Çölkesen F, ed. Primary Immunodeficiency Diseases in Adults. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.115-24.

ABSTRACT
Primary immunodeficiencies are a group of disorders resulting from inborn errors of immunity. In addition to recurrent infections, immundysregulation, lymphoproliferation, and autoimmunity can be a part of their clinical spectrum; and management of these accompanying processes are as important as treating and controlling infections themselves. Targeted therapies are planned to eventually achieve a result in which either an aberrantly active pathway caused by a gain of function variant is silenced, or a deficient molecular process resulted from a loss of function is reinstituted. Biological drugs play a leading role in this personalized treatment modality. This article discusses the pathophysiology of primary immunodeficiencies (PID) accompanied by autoimmunity, genetic changes associated with them, and commonly used biological agents in the treatment.

Keywords: Immunodeficiency; autoimmunity; biological therapy; molecular targeted therapy

Referanslar

  1. Cunningham-Rundles C, Bodian C, Ochs HD, Martin S, Reiter-Wong M, Zhuo Z. Long-term low-dose IL-2 enhances immune function in common variable immunodeficiency. Clinical immunology (Orlando, Fla). 2001;100(2):181-90. [Crossref]  [PubMed]
  2. Moutsopoulos NM, Zerbe CS, Wild T, Dutzan N, Brenchley L, DiPasquale G, et al. Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. The New England journal of medicine. 2017;376(12):1141-6. [Crossref]  [PubMed]  [PMC]
  3. Pinto MV, Neves JF. Precision medicine: The use of tailored therapy in primary immunodeficiencies. Frontiers in immunology. 2022;13:1029560. [Crossref]  [PubMed]  [PMC]
  4. Kiykim A, Ogulur I, Dursun E, Charbonnier LM, Nain E, Cekic S, et al. Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency. The journal of allergy and clinical immunology In practice. 2019;7(8):2790-800.e2715. [Crossref]  [PubMed]  [PMC]
  5. Forbes LR, Vogel TP, Cooper MA, Castro-Wagner J, Schussler E, Weinacht KG, et al. Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations. The Journal of allergy and clinical immunology. 2018;142(5):1665-9. [Crossref]  [PubMed]  [PMC]
  6. Passerini L, Barzaghi F, Curto R, Sartirana C, Barera G, Tucci F, et al. Treatment with rapamycin can restore regulatory T-cell function in IPEX patients. The Journal of allergy and clinical immunology. 2020;145(4):1262-71.e1213. [Crossref]  [PubMed]
  7. Bousfiha A, Moundir A, Tangye SG, Picard C, Jeddane L, Al-Herz W, et al. The 2022 Update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity. Journal of clinical immunology. 2022;42(7):1508-20. [Crossref]  [PubMed]
  8. Ollech A, Mashiah J, Lev A, Simon AJ, Somech R, Adam E, et al. Treatment options for DOCK8 deficiency-related severe dermatitis. The Journal of dermatology. 2021;48(9):1386-93. [Crossref]  [PubMed]
  9. Lan J, Zhang Y, Song M, Cai S, Luo H, OuYang R, et al. Omalizumab for STAT3 Hyper-IgE Syndromes in Adulthood: A Case Report and Literature Review. Frontiers in medicine. 2022;9:835257. [Crossref]  [PubMed]  [PMC]
  10. Abolhassani H, Hammarström L, Cunningham-Rundles C. Current genetic landscape in common variable immune deficiency. Blood. 2020;135(9):656-67. [Crossref]  [PubMed]  [PMC]
  11. Chua I, Standish R, Lear S, Harbord M, Eren E, Raeiszadeh M, et al. Anti-tumour necrosis factor-alpha therapy for severe enteropathy in patients with common variable immunodeficiency (CVID). Clinical and experimental immunology. 2007;150(2):306-11. [Crossref]  [PubMed]  [PMC]
  12. Mannon PJ, Fuss IJ, Dill S, Friend J, Groden C, Hornung R, et al. Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency. Gastroenterology. 2006;131(3):748-56. [Crossref]  [PubMed]
  13. Ruiz de Morales JG, Muñoz F, Hernando M. Successful Treatment of Common Variable Immunodeficiency-associated Inflammatory Bowel Disease With Ustekinumab. Journal of Crohn's and Colitis. 2017;11(9):1154-5. [Crossref]  [PubMed]
  14. Verbsky JW, Hintermeyer MK, Simpson PM, Feng M, Barbeau J, Rao N, et al. Rituximab and antimetabolite treatment of granulomatous and lymphocytic interstitial lung disease in common variable immunodeficiency. The Journal of allergy and clinical immunology. 2021;147(2):704-12.e717. [Crossref]  [PubMed]
  15. Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, et al. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science (New York, NY). 2015;349(6246):436-40. [Crossref]  [PubMed]
  16. Gobert D, Bussel JB, Cunningham-Rundles C, Galicier L, Dechartres A, Berezne A, et al. Efficacy and safety of rituximab in common variable immunodeficiency-associated immune cytopenias: a retrospective multicentre study on 33 patients. British journal of haematology. 2011;155(4):498-508. [Crossref]  [PubMed]  [PMC]
  17. Azizi G, Ahmadi M, Abolhassani H, Yazdani R, Mohammadi H, Mirshafiey A, et al. Autoimmunity in Primary Antibody Deficiencies. International archives of allergy and immunology. 2016;171(3-4):180-93. [Crossref]  [PubMed]
  18. Franxman TJ, Howe LE, Baker JR, Jr. Infliximab for treatment of granulomatous disease in patients with common variable immunodeficiency. Journal of clinical immunology. 2014;34(7):820-7. [Crossref]  [PubMed]
  19. Smith KJ, Skelton H. Common variable immunodeficiency treated with a recombinant human IgG, tumour necrosis factor-alpha receptor fusion protein. The British journal of dermatology. 2001;144(3):597-600. [Crossref]  [PubMed]
  20. Koyasu S. The role of PI3K in immune cells. Nat Immunol. 2003;4(4):313-9. [Crossref]  [PubMed]
  21. Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, et al. Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib. Blood. 2017;130(21):2307-16. [Crossref]  [PubMed]  [PMC]
  22. Lankester AC, Albert MH, Booth C, Gennery AR, Güngör T, Hönig M, et al. EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity. Bone marrow transplantation. 2021;56(9):2052-62. [Crossref]  [PubMed]  [PMC]
  23. Westermann-Clark E, Ballow M, Walter JE. The new quest in CTLA-4 insufficiency: How to immune modulate effectively? The Journal of allergy and clinical immunology. 2022;149(2):543-6. [Crossref]  [PubMed]
  24. Besnard M, Sérazin C, Ossart J, Moreau A, Vimond N, Flippe L, et al. Anti-CD45RC antibody immunotherapy prevents and treats experimental autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. J Clin Invest. 2022;132(7):e156507. [Crossref]  [PubMed]  [PMC]
  25. Teachey DT, Greiner R, Seif A, Attiyeh E, Bleesing J, Choi J, et al. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. British journal of haematology. 2009;145(1):101-6. [Crossref]  [PubMed]  [PMC]
  26. Rao VK, Price S, Perkins K, Aldridge P, Tretler J, Davis J, et al. Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS). Pediatric blood & cancer. 2009;52(7):847-52. [Crossref]  [PubMed]  [PMC]
  27. Condino-Neto A, Newburger PE. Interferon-gamma improves splicing efficiency of CYBB gene transcripts in an interferon-responsive variant of chronic granulomatous disease due to a splice site consensus region mutation. Blood. 2000;95(11):3548-54. [Crossref]  [PubMed]
  28. Frazão JB, Colombo M, Simillion C, Bilican A, Keller I, Wüthrich D, et al. Gene expression in chronic granulomatous disease and interferon-γ receptor-deficient cells treated in vitro with interferon-γ. Journal of cellular biochemistry. 2019;120(3):4321-32. [Crossref]  [PubMed]  [PMC]
  29. Uzel G, Orange JS, Poliak N, Marciano BE, Heller T, Holland SM. Complications of tumor necrosis factor-α blockade in chronic granulomatous disease-related colitis. Clin Infect Dis. 2010;51(12):1429-34. [Crossref]  [PubMed]  [PMC]
  30. Mössner R, Diering N, Bader O, Forkel S, Overbeck T, Gross U, et al. Ruxolitinib Induces Interleukin 17 and Ameliorates Chronic Mucocutaneous Candidiasis Caused by STAT1 Gain-of-Function Mutation. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2016;62(7):951-3. [Crossref]  [PubMed]
  31. Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, et al. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood. 2016;127(25):3154-64. [Crossref]  [PubMed]  [PMC]
  32. Grant A, Gonzalez T, Montgomery MO, Cardenas V, Kerdel FA. Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial. J Am Acad Dermatol. 2010;62(2):205-17. [Crossref]  [PubMed]
  33. Blok JL, Li K, Brodmerkel C, Horvátovich P, Jonkman MF, Horváth B. Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. The British journal of dermatology. 2016;174(4):839-46. [Crossref]  [PubMed]
  34. Prussick L, Rothstein B, Joshipura D, Saraiya A, Turkowski Y, Abdat R, et al. Open-label, investigator-initiated, single-site exploratory trial evaluating secukinumab, an anti-interleukin-17A monoclonal antibody, for patients with moderate-to-severe hidradenitis suppurativa. The British journal of dermatology. 2019;181(3):609-11. [Crossref]  [PubMed]
  35. Wu UI, Holland SM. Host susceptibility to non-tuberculous mycobacterial infections. The Lancet Infectious diseases. 2015;15(8):968-80. [Crossref]  [PubMed]
  36. Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. The New England journal of medicine. 2006;355(6):581-92. [Crossref]  [PubMed]  [PMC]
  37. Broderick L, Hoffman HM. IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting. Nature reviews Rheumatology. 2022;18(8):448-63. [Crossref]  [PubMed]  [PMC]
  38. Sanchez GAM, Reinhardt A, Ramsey S, Wittkowski H, Hashkes PJ, Berkun Y, et al. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. The Journal of clinical investigation. 2018;128(7):3041-52. [Crossref]  [PubMed]  [PMC]
  39. Aeschlimann FA, Batu ED, Canna SW, Go E, Gül A, Hoffmann P, et al. A20 haploinsufficiency (HA20): clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease. Annals of the rheumatic diseases. 2018;77(5):728-35. [Crossref]  [PubMed]
  40. Artac H, Emsen A, Ucaryilmaz H, Emiroglu HH, Uygun V, Stray-Pedersen A. Infliximab therapy for inflammatory colitis in an infant with NEMO deficiency. Immunologic research. 2019;67(4-5):450-3. [Crossref]  [PubMed]
  41. Simonini G, Xu Z, Caputo R, De Libero C, Pagnini I, Pascual V, et al. Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in Blau syndrome-related uveitis. Arthritis and rheumatism. 2013;65(2):513-8. [Crossref]  [PubMed]  [PMC]
  42. Ombrello AK, Qin J, Hoffmann PM, Kumar P, Stone D, Jones A, et al. Treatment Strategies for Deficiency of Adenosine Deaminase 2. The New England journal of medicine. 2019;380(16):1582-4. [Crossref]  [PubMed]  [PMC]
  43. Lee PY, Huang Y, Zhou Q, Schnappauf O, Hershfield MS, Li Y, et al. Disrupted N-linked glycosylation as a disease mechanism in deficiency of ADA2. The Journal of allergy and clinical immunology. 2018;142(4):1363-5.e1368. [Crossref]  [PubMed]  [PMC]
  44. Hashem H, Kumar AR, Müller I, Babor F, Bredius R, Dalal J, et al. Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2. Blood. 2017;130(24):2682-8. [Crossref]  [PubMed]  [PMC]
  45. Socié G, Caby-Tosi MP, Marantz JL, Cole A, Bedrosian CL, Gasteyger C, et al. Eculizumab in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome: 10-year pharmacovigilance analysis. British journal of haematology. 2019;185(2):297-310. [Crossref]  [PubMed]  [PMC]
  46. Pagliuca S, Risitano AM, De Fontbrune FS, Robin M, Iori AP, Marotta S, et al. Combined intensive immunosuppression and eculizumab for aplastic anemia in the context of hemolytic paroxysmal nocturnal hemoglobinuria: a retrospective analysis. Bone marrow transplantation. 2018;53(1):105-7. [Crossref]  [PubMed]
  47. Kawai T, Malech HL. WHIM syndrome: congenital immune deficiency disease. Curr Opin Hematol. 2009;16(1):20-6. [Crossref]  [PubMed]  [PMC]
  48. Merati N, Sivachandran S, Jfri A, Ben-Shoshan M, Vinh DC, Popradi G, et al. Plerixafor on a WHIM - Promise or Fantasy of a New CXCR4 Inhibitor for This Rare, but Important Syndrome? Skin Therapy Lett. 2022 Mar;27(2):1-5.
  49. McDermott DH, Pastrana DV, Calvo KR, Pittaluga S, Velez D, Cho E, et al. Plerixafor for the Treatment of WHIM Syndrome. N Engl J Med. 2019 Jan 10;380(2):163-170. [Crossref]  [PubMed]  [PMC]