Advances in diagnostics for transplant rejection.
Identification of allograft injury, including acute clinical and subclinical injury, is vital in increasing the longevity of the transplanted organ. Acute rejection, which occurs as a result of a variety of immune and non-immune factors including the infiltration of immune cells and antibodies to the donor specific epitopes, poses a significant risk to the organ. Recent years have marked an increase in the discovery of new genomic, transcriptomic, and proteomic biomarkers in molecular diagnostics, which offer better potential for personalized management of the transplanted organ by providing earlier detection of rejection episodes. Areas covered: This review was compiled from key word searches of full-text publications relevant to the field. Expert commentary: Many of the recent advancements in the molecular diagnostics of allograft injury show much promise, but before they can be fully realized further validation in larger sample sets must be conducted. Additionally, for better informed therapeutic decisions, more work must be completed to differentiate between different causes of injury. Moreover, the diagnostics field is looking at methodologies that allow for multiplexing, the ability to identify multiple targets simultaneously, in order to provide more robust biomarkers and better understanding.
a Sarwal Lab , University of California, San Francisco , San Francisco , CA , USA.|b Department of Bioengineering & Therapeutic Sciences , University of California, San Francisco , San Francisco , CA , USA.|c Department of Bioengineering , University of California, Berkeley , Berkeley , CA , USA.
Michael
M
Nasr
a Sarwal Lab , University of California, San Francisco , San Francisco , CA , USA.|d San Francisco Department of Surgery , Unversity of California, San Francisco , San Francisco , CA , USA.
Tara
T
Sigdel
a Sarwal Lab , University of California, San Francisco , San Francisco , CA , USA.|d San Francisco Department of Surgery , Unversity of California, San Francisco , San Francisco , CA , USA.
Minnie
M
Sarwal
D015415:Biomarkers; D019468:Disease Management; D020869:Gene Expression Profiling / Q000379:methods; D023281:Genomics / Q000379:methods; D006084:Graft Rejection / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D025202:Molecular Diagnostic Techniques; D057285:Precision Medicine / Q000379:methods; D040901:Proteomics / Q000379:methods; D014181:Transplantation Immunology
D015415:Biomarkers
Molecular diagnostics; acute rejection; genomics; graft monitoring; indicators of immune response; organ transplantation; personalized transplant management; proteomics; transcriptomics
Nat Rev Immunol. 2003 Jun;3(6):454-62
12776205
J Transplant. 2012;2012:842141
22778908
Nature. 2012 Sep 6;489(7414):57-74
22955616
Transplant Proc. 2000 Feb;32(1):167-8
10701008
Nature. 2001 Feb 15;409(6822):860-921
11237011
PLoS Med. 2014 Nov 11;11(11):e1001759
25386950
Transplantation. 2009 Jun 27;87(12):1814-20
19543058
Transplantation. 2011 Jul 15;92(1):54-60
21516064
Pediatr Transplant. 2011 Feb;15(1):E1-7
21199204
PLoS Comput Biol. 2010 Sep 23;6(9):
20885780
Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13336-41
26460048
Transplant Proc. 2011 Dec;43(10):3669-74
22172823
Nat Immunol. 2003 Nov;4(11):1102-10
14556006
Proteomics Clin Appl. 2015 Apr;9(3-4):322-34
25641774
J Leukoc Biol. 2007 May;81(5):1258-68
17307864
World J Gastroenterol. 2015 Jan 28;21(4):1061-8
25632178
Nat Med. 2000 May;6(5):549-55
10802711
N Engl J Med. 2003 Jul 10;349(2):125-38
12853585
Nat Rev Nephrol. 2010 Oct;6(10):614-28
20736923
N Engl J Med. 2013 Nov 7;369(19):1860-1
24195554
Hum Immunol. 2013 Nov;74(11):1486-90
23876683
Curr Opin Organ Transplant. 2016 Aug;21(4):362-7
27214090
PLoS One. 2014 Dec 09;9(12):e113987
25489845
Am J Transplant. 2012 Feb;12(2):388-99
22081892
Transpl Immunol. 2015 Mar;32(2):61-5
25698648
J Immunol. 1993 Nov 1;151(9):5053-61
8409456
Mol Cell Proteomics. 2014 Feb;13(2):621-31
24335474
Am J Transplant. 2014 Aug;14(8):1912-21
24954576
Am J Transplant. 2012 Jul;12(7):1811-23
22390571
J Exp Med. 2013 Oct 21;210(11):2205-21
24127489
Clin Biochem. 2016 Mar;49(4-5):317-9
26794634
Mol Med Rep. 2014 Jan;9(1):45-50
24154640
Nat Rev Immunol. 2005 Oct;5(10):807-17
16175181
Rev Esp Cardiol. 2011 Dec;64(12):1109-13
21924812
Nature. 2003 Mar 13;422(6928):198-207
12634793
Transpl Int. 2013 Jan;26(1):75-83
23137306
Clin Dev Immunol. 2013;2013:849835
24348683
N Engl J Med. 2011 Feb 3;364(5):485-6; author reply 486
21288109
Nat Methods. 2010 Apr;7(4):287-9
20208531
JAMA. 2011 Mar 23;305(12):1210-6
21427373
Clin J Am Soc Nephrol. 2012 Jun;7(6):1018-25
22498498
Clin Chest Med. 2011 Jun;32(2):295-310
21511091
Am J Transplant. 2012 Oct;12(10):2710-8
23009139
Transplant Proc. 2011 Jun;43(5):1908-12
21693299
Clin Chem. 2015 Dec;61(12):1505-14
26506996
Clin Transpl. 2012;:201-5
23721023
Am J Transplant. 2013 Oct;13(10):2634-44
23968332
J Am Soc Nephrol. 2015 May;26(5):1161-71
25381426
J Allergy Clin Immunol. 2006 Feb;117(2 Suppl Mini-Primer):S430-5
16455341
Heart. 2013 Apr;99(7):445-53
23257172
Transplant Proc. 2012 Jul-Aug;44(6):1533-5
22841205
PLoS One. 2015 Sep 14;10(9):e0138133
26367000
Sci Transl Med. 2014 Jun 18;6(241):241ra77
24944192
Transplantation. 2013 Jul 15;96(1):97-101
23756769
Can J Kidney Health Dis. 2015 Aug 18;2:28
26285614
Nephrourol Mon. 2015 Jan 20;7(1):e24439
25738128
Clin Chem. 2009 Nov;55(11):1958-66
19729469
Transplant Proc. 2015 Mar;47(2):504-10
25769598
J Biol Chem. 2011 Jul 22;286(29):25443-9
21632532
Semin Immunol. 2011 Aug;23(4):235-51
21908202
Transplantation. 1993 May;55(5):993-5
8497913
Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6229-34
21444804
J Heart Lung Transplant. 2005 Jul;24(7 Suppl):S219-26
15993777
Kidney Int. 2016 Jun;89(6):1244-52
27165815
Am J Transplant. 2014 May;14(5):1164-72
24725967
J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S324-35
20176267
Liver Transpl. 2012 Mar;18(3):290-7
21932376
Circ Heart Fail. 2014 May;7(3):463-9
24733367
Clin Transpl. 2003;:449-52
15387129
Electrophoresis. 2005 Apr;26(7-8):1291-305
15765477
J Am Soc Nephrol. 2003 Sep;14(9):2402-10
12937320
Lancet. 1998 May 2;351(9112):1329-30
9643800
Immunol Today. 1999 Feb;20(2):77-82
10098326
Transplant Proc. 2015 Jul-Aug;47(6):1688-91
26293034
J Exp Med. 2008 Dec 22;205(13):3133-44
19047438
Hum Immunol. 2014 Jan;75(1):47-58
24055694
Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5330-5
19289845
Nature. 2002 Jan 31;415(6871):536-41
11823861
Transplantation. 2007 Mar 27;83(6):791-8
17414714
Genome Med. 2011 Jun 08;3(6):37
21658299
Biomark Med. 2012 Jun;6(3):259-71
22731899
Pediatr Nephrol. 2010 Jan;25(1):61-74
21476231
Clin Chem. 1999 Oct;45(10):1741-6
10508119
Am J Physiol Lung Cell Mol Physiol. 2004 Jun;286(6):L1129-39
15136293
Nat Immunol. 2003 Nov;4(11):1093-101
14556005
J Am Soc Nephrol. 2010 Feb;21(2):362-73
20093355
Ann Appl Stat. 2010;4(4):1797-1823
21593992
Nat Med. 2005 Jun;11(6):605-13
15937473
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3373-7
8475083