Plasma Levels of Complement Activation Fragments C3b and SC5b-9 Significantly Increased in Patients with Thrombotic Microangiopathy After Allogeneic Stem Cell Transplantation

Overview

Journal Ann Hematol

Specialty Hematology

Date 2017 Aug 13

PMID 28801815

Citations 28

Authors

Jiaqian Qi

Jie Wang

Jia Chen

Jian Su

Yaqiong Tang

Xiaojin Wu

Xiao Ma

Feng Chen

Changgeng Ruan

X Long Zheng

Depei Wu

Yue Han

Affiliations

Soon will be listed here.

Abstract

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but severe complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, the mechanism is unclear. From 2011 to 2014, 20 patients with TA-TMA, 20 patients without, and 54 patients with various other complications, including veno occlusive disease (VOD), graft-versus-host disease (GVHD), and infection, were recruited in the study. Plasma vWF antigen (vWFAg), vWF activity (vWFAc), and ADAMTS13 activity were determined in these patients by ELISAs and FRETS-vWF73 assay, respectively. Plasma C3b, sC5b-9, and CH50 were also determined by ELISAs. Plasma levels of C3b were significantly increased in patients with either TA-TMA (p < 0.0001) or GVHD (p < 0.01). Plasma sC5b-9 and CH50 levels in patients with TA-TMA were also significantly increased (p < 0.001). Plasma ADAMTS13 activity was lower in patients with VOD, but normal with other complications. Both plasma vWFAg and vWFAc levels were not elevated in patients with TA-TMA or VOD compared with those of other groups. Complement activation likely via an alternative pathway (increased C3b, sC5b-9, and CH50) may play a role in the pathogenesis of TA-TMA. ADAMTS13 activity is reduced in VOD, but the ADAMTS13/vWF axis appears to be unaffected in patients with TA-TMA.

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References

Noris M, Mescia F, Remuzzi G . STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol. 2012; 8(11):622-33. DOI: 10.1038/nrneph.2012.195. View

Cho B, Yahng S, Lee S, Eom K, Kim Y, Kim H . Validation of recently proposed consensus criteria for thrombotic microangiopathy after allogeneic hematopoietic stem-cell transplantation. Transplantation. 2010; 90(8):918-26. DOI: 10.1097/TP.0b013e3181f24e8d. View

George J, Li X, McMinn J, Terrell D, Vesely S, Selby G . Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion. 2004; 44(2):294-304. DOI: 10.1111/j.1537-2995.2004.00700.x. View

Thachil J . Nitric oxide in transplantation-related thrombotic microangiopathy. Bone Marrow Transplant. 2008; 43(6):513-4. DOI: 10.1038/bmt.2008.350. View

Nichols W . Management of infectious complications in the hematopoietic stem cell transplant recipient. J Intensive Care Med. 2004; 18(6):295-312. DOI: 10.1177/0885066603258009. View

Carroll M, Isenman D . Regulation of humoral immunity by complement. Immunity. 2012; 37(2):199-207. PMC: 5784422. DOI: 10.1016/j.immuni.2012.08.002. View

Jodele S, Licht C, Goebel J, Dixon B, Zhang K, Sivakumaran T . Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy. Blood. 2013; 122(12):2003-7. PMC: 3790943. DOI: 10.1182/blood-2013-05-501445. View

Nakamae H, Yamane T, Hasegawa T, Nakamae M, Terada Y, Hagihara K . Risk factor analysis for thrombotic microangiopathy after reduced-intensity or myeloablative allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2006; 81(7):525-31. DOI: 10.1002/ajh.20648. View

Jodele S, Fukuda T, Vinks A, Mizuno K, Laskin B, Goebel J . Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Biol Blood Marrow Transplant. 2013; 20(4):518-25. PMC: 5436705. DOI: 10.1016/j.bbmt.2013.12.565. View

10.

Changsirikulchai S, Myerson D, Guthrie K, McDonald G, Alpers C, Hingorani S . Renal thrombotic microangiopathy after hematopoietic cell transplant: role of GVHD in pathogenesis. Clin J Am Soc Nephrol. 2009; 4(2):345-53. PMC: 2637592. DOI: 10.2215/CJN.02070508. View

11.

Vorup-Jensen T, Boesen T . Protein ultrastructure and the nanoscience of complement activation. Adv Drug Deliv Rev. 2011; 63(12):1008-19. DOI: 10.1016/j.addr.2011.05.023. View

12.

Ho V, Cutler C, Carter S, Martin P, Adams R, Horowitz M . Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005; 11(8):571-5. DOI: 10.1016/j.bbmt.2005.06.001. View

13.

Zhang L, Lawson H, Harish V, Huff J, Knovich M, Owen J . Creation of a recombinant peptide substrate for fluorescence resonance energy transfer-based protease assays. Anal Biochem. 2006; 358(2):298-300. DOI: 10.1016/j.ab.2006.06.022. View

14.

Wehner J, Morrell C, Reynolds T, Rodriguez E, Baldwin 3rd W . Antibody and complement in transplant vasculopathy. Circ Res. 2007; 100(2):191-203. DOI: 10.1161/01.RES.0000255032.33661.88. View

15.

Jodele S, Zhang K, Zou F, Laskin B, Dandoy C, Myers K . The genetic fingerprint of susceptibility for transplant-associated thrombotic microangiopathy. Blood. 2015; 127(8):989-96. PMC: 4828073. DOI: 10.1182/blood-2015-08-663435. View

16.

Jodele S, Laskin B, Dandoy C, Myers K, El-Bietar J, Davies S . A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev. 2014; 29(3):191-204. PMC: 4659438. DOI: 10.1016/j.blre.2014.11.001. View

17.

Tutschka P, Copelan E, Klein J . Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood. 1987; 70(5):1382-8. View

18.

Laskin B, Goebel J, Davies S, Jodele S . Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood. 2011; 118(6):1452-62. DOI: 10.1182/blood-2011-02-321315. View

19.

Zheng X . ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura. Annu Rev Med. 2015; 66:211-25. PMC: 4599565. DOI: 10.1146/annurev-med-061813-013241. View

20.

Peyvandi F, Siboni S, Lambertenghi Deliliers D, Lavoretano S, De Fazio N, Moroni B . Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation. Br J Haematol. 2006; 134(2):187-95. DOI: 10.1111/j.1365-2141.2006.06126.x. View