Antibody Mediated Rejection in Liver Transplantation

*Product Information

Product Description Cat Id Tests

LABScreen® Single Antigen (For In Vitro Diagnostic Use.)

Idiopathic fibrosis progression
LABScreen Single Antigen HLA Class I - Combi LS1A04 25 tests
LABScreen Single Antigen HLA Class II - Group 1 LS2A01 25 tests
Graft injury (normal or mild hepatic profile)
LABScreen® Single Antigen Supplement (For In Vitro Diagnostic Use.)
LABScreen Single Antigen Class I - Supplement (Group1) LS1ASP01 25 tests
LABScreen Single Antigen Class II - Supplement (Group1) LS2ASP01 25 tests Diffuse portal C4d detectable in the liver graft

C1qScreen™ (For In Vitro Diagnostic Use. (European Union Only))

C1qScreen™ C1Q 25 tests Preformed or de novo DSA detectable in circulation after LT

C1qScreen Class I Positive Control C1QS-PC1 20 tests

C1qScreen Negative Control Serum C1QS-NC 20 tests
Liver transplant Time Graft lost
C1qScreen Class II Positive Control C1QS-PC2 20 tests

Figure 1. Hypothetical chain of events for idiopathic fibrosis progression.

DSA – Donor-specific anti-HLA antibodies; LT – Liver transplantation. (Adapted from: Cuadrado A at
References al. Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation. World J
Gastroenterol. 2015 Oct 21;21(39):11016-26)
1. Cuadrado A, San Segundo D, López-Hoyos M, Crespo J, Fábrega E. Clinical significance of donor-specific human leukocyte antigen
antibodies in liver transplantation. World J Gastroenterol. 2015 Oct 21;21(39):11016-26
2. O'Leary JG, Demetris AJ, Friedman LS, Gebel HM, Halloran PF, Kirk AD, Knechtle SJ, McDiarmid SV, Shaked A, Terasaki PI, Tinckam KJ,
Tomlanovich SJ, Wood KJ, Woodle ES, Zachary AA, Klintmalm GB. The role of donor-specific HLA alloantibodies in liver transplantation.
Am J Transplant. 2014 Apr;14(4):779-87
3. Kim PT, Demetris AJ, O'Leary JG. Prevention and treatment of liver allograft antibody-mediated rejection and the role of the 'two-hit
hypothesis'. Curr Opin Organ Transplant. 2016 Apr;21(2):209-18
4. O'Leary JG, Cai J, Freeman R, Banuelos N, Hart B, Johnson M, Jennings LW, Kaneku H, Terasaki PI, Klintmalm GB, Demetris AJ.
Proposed Diagnostic Criteria for Chronic Antibody-Mediated Rejection in Liver Allografts. Am J Transplant. 2016 Feb;16(2):603-14
5. Ducreux S, Guillaud O, Bosch A, Thaunat O, Morelon E, Hervieu V, Mekki Y, Boillot O, Scoazec JY, Dubois V, Dumortier J. Monitoring
efficiency of humoral rejection episode therapy in liver transplantation: any role for complement binding Luminex Single Antigen assays?
Transpl Immunol. 2016 Mar;35:23-8
6. Levitsky J, Kaneku H, Jie C, Walsh RC, Abecassis M, Tambur AR. Donor-Specific HLA Antibodies in Living vs. Deceased Donor Liver
Transplant Recipients. Am J Transplant. 2016 Feb 20
7. Wozniak LJ, Hickey MJ, Venick RS, Vargas JH, Farmer DG, Busuttil RW, McDiarmid SV, Reed EF. Donor-specific HLA Antibodies Are
Associated With Late Allograft Dysfunction After Pediatric Liver Transplantation. Transplantation. 2015 Jul;99(7):1416-22
8. Demetris AJ, Zeevi A, O'Leary JG. ABO-compatible liver allograft antibody-mediated rejection: an update. Curr Opin Organ Transplant. 2015
Jun;20(3):314-24

*Products not cleared for the treatment or mitigation of AMR.

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MKT-MATERIAL-34
 Antibody Mediated Rejection in Liver Transplantation

The recognition of antibody mediated rejection (AMR) in liver allografts has been an important subject of The two-hit hypothesis of AMR in liver transplantation is different for acute and chronic rejection. Acute AMR
discussion. Although liver allografts are relatively resistant to AMR compared to other solid organs, findings requires preformed high titer HLA class I DSA and is usually associated with marginal donors or high MELD patients.
from the last decade have demonstrated that they are still susceptible. Early acute AMR is rare occurring in Chronic AMR occurs in the presence of HLA class II DSA and presents an injury that increases HLA class II
highly sensitized recipients, representing less than 1% of all liver transplants. However, chronic AMR in the expression in the organ.
setting of de novo HLA class II donor specific antibodies (DSA) presents an incidence between 8-15% and has
been associated with specific characteristics of antibodies that could be easily identified with Solid Phase
Antibody testing. Better characterization of those DSA phenotypes in randomized controlled trials may identify C C
C C
other potential associations of DSA with liver transplantation outcomes
C Lymphocyte Under C
quiescent
conditions class
IIexpression is
minimal.Injury
upregulates
U U class II UU UU U UUU U UUU
Hyperacute rejection expression in
Acute antibody-mediated rejection the liver
Early acute “cellular” rejection allograft
Steroid-resistant rejection
Antibody-mediated renal allograft rejection in
simultaneous liver-kidney transplant recipients C DSA with Dense class II expression facilitates class II
Fc binding receptor Hepatocyte DSA binding. Complement fixing antibodies
(subclass dependent, IgG3 is the strongest
DSA without
complement fixing antibody of the subclasses)
Fc binding receptor
DSA

may activate complement

Chronic rejection U MHC class II Liver Sinusoidal
Idiopathic fibrosis progression Endothelial cell
Accelerated fibrosis in hepatitis C virus

De novo autoimmune hepatitis

Antibodies with
Anastomotic biliary strictures Fc binding
Portal venopathy and nodular regenerative hyperplasia receptors may
C C facilitate C C
antibody
UU UU U UUU U UUU dependent UU UU U UUU U UUU
cellular
Figure 2. Potential associations of anti-HLA DSA with outcomes in liver transplantation.
cytotoxicity
HLA – Human leukocyte antigen; DSA: Donor-specific anti-HLA antibodies. (Adapted from: (ADCC).
1. O'Leary JG et al. The role of donor-specific HLA alloantibodies in liver transplantation. Am J Transplant. 2014
Apr;14(4):779-87. 2. Cuadrado A et al. Clinical significance of donor-specific human leukocyte antigen antibodies in
liver transplantation. World J Gastroenterol. 2015 Oct 21;21(39):11016-26)

Figure 3. The two-hit hypothesis of liver allograft antibody-mediated rejection. (Reproduced from: Kim PT, Demetris AJ, O’Leary
JG. Prevention and treatment of liver allograft antibody-mediated rejection and the role of the 'two-hit hypothesis'. Curr Opin Organ Transplant. 2016
Apr;21(2):209-18)