Natural complement regulators are required for control of the complement system1,2

  • Complement activation is continuously occurring3-6
  • Complement can be amplified by everyday occurrences such as bacterial and viral infections, allergies, and other trauma4,7-9

aHUS results from chronic, uncontrolled complement activity that leads to progressive and life-threatening complications13

While identification of a specific mutation can have prognostic implications, mutation identification overall has no impact on clinical outcome14,15

  • 30%-50% of patients with aHUS have no currently identifiable genetic mutation16,17
The number of new genetic abnormalities discovered in patients with aHUS continues to increase over time14,18-20

* Mutations consisted of membrane cofactor protein (MCP), complement factor H (CFH), and factor I (CFI). No mutation identified: n=81. Mutation identified: n=60.14,15

Mutations consisted of MCP, CFH, CFI, complement component 3 (C3), and thrombomodulin (THBD). No mutation identified: n=119. Mutation identified: n=116.14,15

Regardless of whether or not a mutation is identified, patients with aHUS have similarly devastating outcomes14,15

Identification of genetic complement mutations is not required for aHUS diagnosis or management decisions21,22

1. Noris M, et al. Nat Rev Nephrol. 2012;8(11):622-633. 2. Loirat C, et al. Pediatr Nephrol. 2008;23(11):1957-1972. 3. Loirat C, et al. Presse Med. 2012;41(3 Pt 2):e115-e135. 4. Ricklin D, et al. Nat lmmunol. 2010;11(9):785-797. 5. Nester CM, Thomas CP. Hematology Am Soc Hematol Educ Program. 2012;2012:617-625. 6. Barbour T, et al. Nephrol Dial Transplant. 2012;27(7):2673-2685. 7. Hirt-Minkowski P, et al. Nephron Clin Pract. 2010;114(4):c219-c235. 8. Wagner E, Frank MM. Nat Rev Drug Discov. 2010;9(1):43-56. 9. Liszewski MK, Atkinson JP. Hematology Am Soc Hematol Educ Program. 2011 ;2011 :9-14. 10. Campistol JM, et al. Nefrologia. 2015;35(5):421-447. 11. Jokiranta TS. Blood. 2017;129(21):2847-2856. 12. Maga TK, et al. Hum Mutat. 2010;31(6):E1445-E1460. 13. Goodship THJ, et al. Kidney Int. 2017;91(3):539-551. 14. Noris M, et al. Clin J Am Soc Nephrol. 2010;5(10):1844-1859. 15. Caprioli J, et al. Blood. 2006;108(4):1267-1279. 16. Kavanagh D, Goodship THJ. Hematology Am Soc Hematol Educ Program. 2011 ;2011:15-20. 17. Kavanagh D, et al. Br Med Bull. 2006;77-78:5-22. 18. Bu F, et al. J Am Soc Nephrol. 2014;25(1):55-64. 19. George JN, et al. N Engl J Med. 2014;371(7):654-666. 20. Structural Immunology Group. Database of complement gene variants. http://www.complement-db.org/advance_search_results.php?dosearch=1&source= lab&dosearch=1&source=lab&genead%5B%5D=all&reference=&condition%5B%5D=aHUS&cutoff=0.01. Accessed May 15, 2018. 21. Laurence J, et al. Clin Adv Hematol Oncol. 2016;14 Suppl 11(11):2-15. 22. Azoulay E, et al. Chest. 2017;152(2):424-434.