非典型溶血性尿毒症症候群（aHUS） 診断から治療 …

1 2015 1 1 aHUS aHUS aHUS aHUS 2aHUS 2013 atypical hemolytic uremic syndrome aHUS 1 1aHUS aHUS 1 2 3 3 TMA) HUS) TTP) TMA HELLP TMA HUS TTP TMA aHUS aHUS 100 2 3 100 7 aHUS 2015 100 aHUS aHUS 3 aHUS C3 C3a C3b C3b B complement factor B CFB D complement factor D CFD 3 C3 C3bBb C3 C3 C3a C3b

2 C3b C5 C3bBbC3b C5 C5 C5a C5b C5b C6-C9 membrane attack complex MAC 2 C3 C3b C3b H complement factor H CFH membrane cofactor protein MCP CD46 I complement factor I CFI C3b aHUS CFH CFI CD46 factor H CFH aHUS CFB C3 aHUS aHUS C3a C5 C5a C5b-9 C3bC3 iC3bC3 + H2O C5 C5b C6 C7C8C9 C3 CFB H I MCP C3 2 aHUS 1.

3 Noris M, Mescia F, Remuzzi G. Nat Rev Nephrol. 2012;8:622-633. 2. Leban N, Abarrategui-Garrido C, Fariza-Requejo E, et al. Int J ;39:110-113. 3. Hirt-Minkowski P, Dickenmann M, Schifferli JA. Nephron Clin Pract. 2010;114:c219-c235. 4. Loirat C, Noris M, Fremeaux-Bacchi V. Pediatr Nephrol. 2008;23 3 aHUS aHUS 2 aHUS aHUS aHUS 4 aHUS 8 10 CFH CFH C CFH C3b CFH CFH CFH CFH comple- ment factor H Related CFHR 1 5 CFH CFH CFHR

4 CFH aHUS DEAP-HUS DEficiency of CFHR plasma proteins and Autoantibody Positive form of 1. Noris M and Remuzzi G. Nat Rev Nephrol. 2014; 10 3 : 174-80. 2. Laurence J. Clin Adv Hematol Oncol. 2012; 10 suppl 17 : 1-12. 3. Legendre CM, Licht C, Muus P, et al. N Engl J Med. 2013; 368: 2169-2181. 4. Sellier-Leclerc A-L, Fr meaux-Bacchi V, Dragon-Durey MA, et al; French Society of Pediatric Nephrology. J Am Soc Nephrol. 2007; 18: 2392-2400. 5. Nester CM, Thomas CP. Hematology Am Soc Hematol Educ Program. 2012; 2012: 617-625. 3 TMA 1 2-5 TMA 2-5 C5a vWF TMA C5b-95 TMA 4aHUS 2 Tsai HM.

5 Transfus Med Rev. 2014; 28 4 : Uremic Syndrome CFHR3-CFHR1 CFHR homology TMA DGKE diacylglycerol kinase epsilon C3b CFH C3b DGKE TMA TMA aHUS TMA TMA DGKE TMA TMA 6aHUS aHUS 1 Hb 10 g/dL 2 15 / L 3

6 HUS HUS aHUS O157 5 aHUS 1. Muus P, et al. Presented at: 18th Congress of the European Hematology Association. June 13-16, 2013; Stockholm, Sweden. Abstract B1774. 2. Neuhaus TJ, et al. Arch Dis Child. 1997; 76: 518-521. 3. Ohanian M, et al. Clin Pharmacol . 2011; 3: 5-12. 4. Noris M, et al. Clin J Am Soc Nephrol. 2010; 5: 1844-1859. 5. Sall e M, et al. Nephrol Dial Transplant. 2010; 25: 2028-2032. 6. Kavanagh D, et al. Br Med Bull. 2006; 77-78: 5-22. 7. Loirat C, et al. Pediatr Nephrol.

7 2008; 23: 1957-1972. 8. Langman CB. Haematologica. 2012; 97 suppl1 : 195-196. 9. Dragon-Durey M-A, et al. J Am Soc Nephrol. 2010; 21: 2180-2187. 10. Zuber J, et al. Nat Rev Nephrol. 2011; 7 1 : 23-35. 11. Caprioli J, et al; for the International Registry of Recurrent and Familial HUS/TTP. Blood. 2006; 108: 1267-1279. 12. St hl A-L, et al. Blood. 2008; 111: 5307-5315. 13. Ariceta G, et al; for the European Paediatric Study Group for HUS. Pediatr Nephrol. 2009; 24: 687-696. 14. Sellier-Leclerc A-L, et al; French Society of Pediatric Nephrology. J Am Soc Nephrol. 2007; 18: 2392-2400.

8 15. Laurence J. Clin Adv Hematol Oncol. 2012; 10 suppl 17 : 1-12. 5aHUS 48% 2 3 4 243% 2 5 6 734% 137% 8 3 3 9 4 7 10 950% ESRD 11 12,13 4,12 eGFR 7,13 2aHUS TMA 8,10,11,15 5 14 5 30 17 aHUS aHUS aHUS 2013 9 C5 aHUS C5 MAC DGKE aHUS aHUS 1

9 8 Fan X, et al. Mol Immunol. 2013; 54: T, et al. Thromb Haemost. 2015; 114. Epub ahead of print 1aHUS CFHF actor H 20 30 10% 60 70 80 80 90 CFHR1/3 Factor HR1, R3 H 6% 6% 70 30 40 20 CD46 MCP Membrane cofactor protein 10 15 13% 20 15 20 CFlFactor lCo-factor 4 10 0% 30 40 60 70 70 80 CFBF actor BC3 convertase 1 2 30 70%1 C3 Complement C3C3b 5 10 43% 40 50 60% 40 50 THBDT hrombomodulinC3b 5% 60 60%1 DGKED iacylglycerol kinase epsilonDAG 2013 13 2015 1 20 3 1 PLGP lasminogen 5 9aHUS 2 aHUS

10 HUS TTP TMA HELLP TMA 6 2013 aHUS 7 TMA HUS TMA aHUS TTP aHUS ADAMTS13 10 TMA HUS TTP TMA 6 HUS TTP aHUS 7 2013 aHUS Definite TTP Hb10g/dL Hb LDH PLT 15 / L AKI 4 AKI Probable AKI 3 2 TTP.