Normal Expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in LPS-responsive and beige-like anchor protein (LRBA) Patient

Document Type : Case Report

Author

1- Reproductive Immuology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Irann

10.22034/igj.2020.245520.1046

Abstract

Bialelic LRBA mutations leads to an Immune dysregulation disorder which name is LRBA deficiency. A wide spectrum of clinical manifestation associated with recurrent infections, enteropathy, hypogammaglobulinemia, and autoimmune manifestations. LRBA interacts with CTLA-4 within recycling it to the T-cell surface. Accordingly, LRBA deficiency abolish CTLA4 protein expression. In this study, we present a case with homozygous mutation in LRBA gene and normal level of CTLA4 protein. This patient revelaed low immunoglobulin levels, CD4+ cells, and CD19+ cells.

Keywords


 1. Habibi S, Zaki-Dizaji M, Rafiemanesh H, Lo B, Jamee M, Gamez-Diaz L, et al. Clinical, Immunologic, and Molecular Spectrum of Patients with LPS-Responsive Beige-Like Anchor Protein Deficiency: A Systematic Review. J Allergy Clin Immunol Pract. 2019;7(7):2379-86 e5. 2. Azizi G, Abolhassani H, Zaki-Dizaji M, Habibi S, Mohammadi H, Shaghaghi M, et al. Polyautoimmunity in Patients with LPS-Responsive Beige-Like Anchor (LRBA) Deficiency. Immunol Invest. 2018;47(5):457-67. 3. Azizi G, Abolhassani H, Habibi S, Rahamooz T, Mohammadi H, Jafarnezhad-Ansariha F, et al. Two Faces of LRBA Deficiency in Siblings: Hypogammaglobulinemia and Normal Immunoglobulin Levels. J Investig Allergol Clin Immunol. 2018;28(1):48-50. 4. Azizi G, Abolhassani H, Yazdani R, Mohammadikhajehdehi S, Parvaneh N, Negahdari B, et al. New therapeutic approach by sirolimus for enteropathy treatment in patients with LRBA deficiency. Eur Ann Allergy Clin Immunol. 2017;49(5):235-9. 5. Alkhairy OK, Abolhassani H, Rezaei N, Fang M, Andersen KK, Chavoshzadeh Z, et al. Spectrum of Phenotypes Associated with Mutations in LRBA. J Clin Immunol. 2016;36(1):33-45. 6. Lopez-Herrera G, Tampella G, Pan-Hammarstrom Q, Herholz P, Trujillo-Vargas CM, Phadwal K, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet. 2012;90(6):986-1001. 7. Azizi G, Mirshafiey A, Abolhassani H, Yazdani R, Ghanavatinejad A, Noorbakhsh F, et al. The imbalance of circulating T helper subsets and regulatory T cells in patients with LRBA deficiency: Correlation with disease severity. J Cell Physiol. 2018;233(11):8767-77. 8. Salami F, Shirkani A, Shahrooei M, Azizi G, Yazdani R, Abolhassani H, et al. Leishmaniasis and Autoimmunity in Patient with LPS-Re-sponsive Beige-Like Anchor Protein (LRBA) Deficiency. Endocr Metab Immune Disord Drug Targets. 2020;20(3):479-84. 9. Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P, Yazdani R, et al. Clinical, immunologic, molecular analyses and outcomes of iranian patients with LRBA deficiency: A longitudinal study. Pediatr Allergy Immunol. 2017;28(5):478-84. 10. Rowshanravan B, Halliday N, Sansom DM. CTLA-4: a moving target in immunotherapy. Blood. 2018;131(1):58-67. 11. Lo B, Abdel-Motal UM. Lessons from CTLA4 deficiency and checkpoint inhibition. Curr Opin Immunol. 2017;49:14-9. 12. Alroqi FJ, Charbonnier LM, Baris S, Kiykim A, Chou J, Platt CD, et al. Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation. J Allergy Clin Immunol. 2018;141(3):1050-9 e10. 13. Kostel Bal S, Haskologlu S, Serwas NK, Islamoglu C, Aytekin C, Kendirli T, et al. Multiple Presentations of LRBA Deficiency: a Single-Center Experience. J Clin Immunol. 2017;37(8):790-800. 14. 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. 2015;349(6246):436-40. 15. Martínez Jaramillo C, Trujillo-Vargas CM. LRBA in the endomembrane system. Colomb Med (Cali). 2018;49(3):236-43. 16. Cepika AM, Sato Y, Liu JM, Uyeda MJ, Bacchetta R, Roncarolo MG. Tregopathies: Monogenic diseases resulting in regulatory T-cell deficiency. J Allergy Clin Immunol. 2018;142(6):1679-95. 17. De Bruyne M, Bogaert DJ, Venken K, Van den Bossche L, Bonroy C, Roels L, et al. A novel LPS-responsive beige-like anchor protein (LRBA) mutation presents with normal cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and overactive T(H)17 immunity. J Allergy Clin Immunol. 2018;142(6):1968-71. 18. Gámez-Díaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG, Noriko M, et al. The extended phenotype of LPS-responsive beigelike anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016;137(1):223-30. 19. Tesi B, Priftakis P, Lindgren F, Chiang SC, Kartalis N, Löfstedt A, et al. Successful Hematopoietic Stem Cell Transplantation in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Gene Mutation. J Clin Immunol. 2016;36(5):480-9. 20. Azizi G, Jamee M, Yazdani R, Bagheri Y, Fayyaz F, Jadidi-Niaragh F, et al. CTLA-4 Expression in CD4+ T Cells From Patients With LRBA Deficiency and Common Variable Immunodeficiency With No Known Monogenic Disease. J Investig Allergol Clin Immunol. 2018;28(6):422-4. 21. Burnett DL, Parish IA, Masle-Farquhar E, Brink R, Goodnow CC. Murine LRBA deficiency causes CTLA-4 deficiency in Tregs without progression to immune dysregulation. Immunol Cell Biol. 2017;95(9):775-88. 22. De Bruyne M, Bogaert DJ, Venken K, Van den Bossche L, Bonroy C, Roels L, et al. A novel LPS-responsive beige-like anchor protein (LRBA) mutation presents with normal cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and overactive TH17 immunity. J Allergy Clin Immunol. 2018;142(6):1968-71. 23. Burnett DL, Parish IA, Masle-Farquhar E, Brink R, Goodnow CC. Murine LRBA deficiency causes CTLA-4 deficiency in Tregs without progression to immune dysregulation. Immunol. Cell Biol 2017;95(9):775-88. 24. De Bruyne M, Bogaert DJ, Venken K, Van den Bossche L, Bonroy C, Roels L, et al. A novel LPS-responsive beige-like anchor protein (LRBA) mutation presents with normal cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and overactive TH17 immunity. J Allergy Clin Immunol . 2018; 142(6):1968-71.