Ecto-5′nucleotidase (CD73) May Predict Occurrence and Grade of GVHD in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Authors

  • Rasha I. Ibrahim Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • Maha El- Zimaity Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • Nevine N. Moustafa Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • Mohamed Hamdi Attia Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • Walaa A. Elsalakawy Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • Rana Z. Abass Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt

DOI:

https://doi.org/10.3889/oamjms.2021.5707

Keywords:

Ecto-5′nucleotidase (CD73), Graft versus host disease, allogeneic HSCT

Abstract

BACKGROUND: Graft versus host disease (GVHD) represents a main cause of post-transplant morbidity and mortality. Ectonucleotidases are one of major components of purinergic signaling which is one of the important mediator pathways regulating cellular functions. CD73 is the most significant member of ectonucleotidases.

AIM: The aim of the study was to assess role of CD73 in development/severity of GVHD among patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT)

SUBJECT AND METHODS: This is a prospective study conducted on 30 adult patients eligible for allogeneic HSCT and their 30 donors in a period of 2 years from January 2015 until January 2017. Assessment of CD73 positive cells through flow cytometry on peripheral blood samples in donors during assessment period before receiving G-CSF and in recipients before conditioning at day −7 and once GVHD occurs (within 12 months) or at end of follow-up period was done.

RESULTS: CD73 level was significantly higher in recipients pre/post-transplantation (58.24 ± 19.68, 65.78 ± 19.03 respectively) than in donors (29.08 ±14.14) (p = 0.022), there is a significant negative correlation between pre-transplant CD73 level in recipients and occurrence of chronic GVHD (cGVHD), (p = 0.004) and its grade (p = 0.0496). Ectonucleotidase CD73 expression in recipients was a good predictor of cGVHD with sensitivity of 100% and Specificity of 65% at cut off value ≤61.07%. CD73 expression in recipients was independently predicting cGVHD.

CONCLUSION: CD 73 may represent a promising, clinically applicable tool of predicting cGVHD and its grade in patients undergoing HSCT.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Robbie N, Deborah T. Hematopoietic stem cell transplantation. In: Tomlinson D, Kline NE, editors. Pediatric Oncology Nursing. Advanced Clinical Hand Book. 2nd ed., Ch. 3. Germany: Springer; 2010. p. 243-67.

Apostolova P, Zeiser R. The Role of purine metabolites as DAMPs in acute graft-versus-host disease. Front Immunol. 2016;7:439. https://doi.org/10.3389/fimmu.2016.00439 PMid:27818661

Martin B, Deeg H. acute graft versus host disease. In: Soiffer RJ, editor. Hematopoietic Stem Cell Transplantation. 2nd ed., Vol. 1, Ch. 25. United States: Humana Press; 2008. p. 589-620. https://doi.org/10.1007/978-1-59745-438-4_25 PMid:25709759

Marks C, Stadler M, Häusermann P, Wolff D, Buchholz S, Stary G, et al. German-Austrian-Swiss consensus conference on clinical practice in chronic graft-versus-host disease (GVHD): Guidance for supportive therapy of chronic cutaneous and musculoskeletal GVHD. Br J Dermatol. 2011;165(1):18-29. https://doi.org/10.1111/j.1365-2133.2011.10360.x PMid:21466534.

Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373(9674):1550-61. https://doi.org/10.1016/s0140-6736(09)60237-3 PMid:19282026

Atkinson K, Horowitz MM, Gale RP, van Bekkum DW, Gluckman E, Good RA, et al. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood. 1990;75(12):2459-64. https://doi.org/10.1182/blood.v75.12.2459.bloodjournal75122459 PMid:2350582

Robson SC, Sévigny J, Zimmermann H. The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance. Purinergic Signal. 2006;2(2):409-30. https://doi.org/10.1007/s11302-006-9003-5 PMid:18404480

Antonioli L, Pacher P, Vizi ES, Haskó G. CD39 and CD73 in immunity and inflammation. Trends Mol Med. 2013;19(6):355-67. https://doi.org/10.1016/j.molmed.2013.03.005 PMid:23601906

Zhang B. CD73 promotes tumor growth and metastasis. Oncoimmunology. 2012;1(1):67-70. https://doi.org/10.4161/onci.1.1.18068 PMid:22720214

Tsukamoto H, Chernogorova P, Ayata K, Gerlach UV, Rughani A, Ritchey JW, et al. Deficiency of CD73/ecto-5’-nucleotidase in mice enhances acute graft-versus-host disease. Blood. 2012;119(19):4554-64. https://doi.org/10.1182/blood-2011-09-375899 PMid:22262774

Thompson LF, Tsukamoto H, Chernogorova P, Zeiser R. A delicate balance: CD73-generated adenosine limits the severity of graft vs. host disease but also constrains the allogeneic graft vs. tumor effect. Oncoimmunology. 2013;2(1):e22107. https://doi.org/10.4161/onci.22107 PMid:23482243

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on Acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825-8. PMid:7581076

Carpenter PA, Kitko CL, Elad S, Flowers ME, Gea-Banacloche JC, Halter JP, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: V. The 2014 ancillary therapy and supportive care working group report. Biol Blood Marrow Transplant. 2015;21(7):1167-87. https://doi.org/10.1016/j.bbmt.2015.03.024 Mid:25838185

Bastid J, Cottalorda-Regairaz A, Alberici G, Bonnefoy N, Eliaou JF, Bensussan A. ENTPD1/CD39 is a promising therapeutic target in oncology. Oncogene. 2013;32(14):1743-51. https://doi.org/10.1038/onc.2012.269 PMid:22751118

Zhao SX, Zhang HM, Dong SX, Liu JH, Zhou Z, Wang HJ, et al. Characteristics and clinical significance of CD73 expression in subtypes of leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2011;19(5):1141-4. PMid:22040959

Samanta D, Park Y, Ni X, Li H, Zahnow CA, Gabrielson E, et al. Chemotherapy induces enrichment of CD47+/CD73+/PDL1+ immune evasive triple-negative breast cancer cells. Proc Natl Acad Sci USA. 2018;115(6):E1239-48. https://doi.org/10.1073/pnas.1718197115 PMid:29367423

Jacobsohn DA, Vogelsang GB. Acute graft versus host disease. Orphanet J Rare Dis. 2007;2:35. https://doi.org/10.1186/1750-1172-2-35 PMid:17784964

Krstevska S, Genadieva-Stavric S, Pivkova A, Stojanovski Z, Georgievski B, Balkanov T. Acute graft versus host disease in hematopoietic stem cell alotransplant recipients. Med Arh. 2011;65(5):260-4. https://doi.org/10.5455/medarh.2011.65.260-264 PMid:22073847

Villarreal CD, Alanis JC, Pérez JC, Candiani JO. Cutaneous graft-versus-host disease after hematopoietic stem cell transplant-a review. An Bras Dermatol. 2016;91(3):336-43. https://doi.org/10.1590/abd1806-4841.20164180 PMid:27438202

Cutler C, Antin JH. Manifestations and treatment of acute graft-versus-host disease. In: Frederick RA, Stephen JF, Robert SN, Karl GB, editors. Thomas’ Hematopoietic Cell Transplantation. 4th ed., Ch. 86. United States: Wiley Blackwell; 2009. p. 1287-303. https://doi.org/10.1002/9781444303537.ch86

Wang L, Fan J, Chen S, Zhang Y, Curiel TJ, Zhang B. Graft-versus-host disease is enhanced by selective CD73 blockade in mice. PLoS One. 2013;8(3):e58397. https://doi.org/10.1371/journal.pone.0058397 PMid:23520507

Lee SJ, Flowers ME. Recognizing and managing chronic graft-versus-host disease. Hematology Am Soc Hematol Educ Program. 2008:134-41. https://doi.org/10.1182/asheducation-2008.1.134 PMid:19074071

Min CK. The pathophysiology of chronic graft-versus-host disease: The unveiling of an enigma. Korean J Hematol. 2011;46(2):80-7. https://doi.org/10.5045/kjh.2011.46.2.80 PMid:21747879

Downloads

Published

2021-02-18

How to Cite

1.
Ibrahim RI, Elzimaity M, Moustafa NN, Attia MH, Elsalakawy WA, Abass RZ. Ecto-5′nucleotidase (CD73) May Predict Occurrence and Grade of GVHD in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. Open Access Maced J Med Sci [Internet]. 2021 Feb. 18 [cited 2024 Mar. 28];9(B):154-60. Available from: https://oamjms.eu/index.php/mjms/article/view/5707