CASE 4 :

A man with kidney

transplantation
 1

Patient's history
ABO/Rh typing HLA Typing
Recipient
O, Rh+ A3/A11, B5/B35/B51(5), Bw4/Bw6, Cw1/Cw4, DR1 DQ1/DQ5

assessed by a doctor to receive kidney

He has a chronic renal disease
transplantation

ABO/Rh typing HLA Typing

O, Rh+ A3/A19(32), B5(51)/B18 Bw4/Bw6, Cw7, DR1/DR9/DR53 DQ1/DQ3

st
1 Donor B-lymphocyte crossmatch Bead-based Panel Reactive
10 years
T-lymphocyte

crossmatch (CDC) (AHG-CDC) Antibody (PRA)

Negative Negative
Negative

Rejection of organs with

A 59-year-old man
Chronic vascular Rejection
 2

Patient's history
Rejection of organs with Patients have been treated with dialysis for a while.
Chronic vascular Rejection

The doctor estimates that the organ transplantation must be

repeated by using the kidneys from the patient's wife.

Physical examination Results Hematology test Results Reference Range

Pulse 75/min CRP 14 mg/L 0-8

Blood pressure 145/88 mmHg Creatinine 9.9 mg/dl 0.7-1.5

Temperature 38.8 °C

Respiratory rate 16 /min

2
BMI 36.5 Kg/m
 Patient's history 3

nd
2 Donor Pre-transplantation
Post-transplantation
nd
Recipient 2 donor
ABO/Rh typing : O, Rh+ ABO/Rh typing : O, Rh+
The urine volume in the first 3 hours remained
normal and began to decrease.
HLA Typing : T-lymphocyte crossmatch : negative
• A2
Cold, headache, muscle pain, nausea and
vomiting (CDC)
• B44(12)/B60(49)
• Cw3/Cw5 Renal arteries and blood circulating are normal
B-lymphocyte crossmatch : negative
• DR1/DR3/DR9/DR13 DQ2/DQ6
but the patient hasacute renal failure and acute (AHG-CDC)
organ rejection.
T-lymphocyte crossmatch : negative Bead-based Panel Reactive Antibody : negative
(CDC) (PRA)

B-lymphocyte crossmatch : positive Hyperacute rejection

(AHG-CDC)

Bead-based Panel Reactive Antibody : Anti-HLA-A32

(PRA)

Tissue biopsy acute humoral rejection edematous

acute tubular necrosis flaccid
thromboembolic event cyanotic
 4

LO 01
 5

Chronic Rejection
Chronic kidney transplant rejection (CKTR)

Chronic kidney transplant rejection (CKTR) is characterized by progressive decrease of

renal graft function that starts to manifest at one-year after the transplantation and

usually accompanied by hypertension and proteinuria

CKTR usually occurs in patients with insufficient immunosuppression or medication

nonadherence
While Persistent allogeneic immune response remains a major cause multiple risk

factors, e.g. early ischemia reperfusion injury, acute rejection episodes and

transplant infectious diseases, can contribute to the development and progression

of CKTR.
 6

Mechanisms of graft rejection :

Chronic Rejection

http://perspectivesinmedicine.cshlp.org/content/3/11/a015461.full https://jasn.asnjournals.org/content/12/3/574/F3

Antibodies can also bind to the surface molecules of target cells and recruit other

cells by interactions via their constant domain

 7

Hyperacute Rejection
Hyperacute rejection is the result of specific recurrent antidonor
antibodies against human leukocyte antigen (HLA), ABO, or other
antigens. Irreversible rapid destruction of the graft occurs.
Histologically there is glomerular thrombosis, fibrinoid necrosis,
and polymorphonuclear leukocyte infiltration.
 8

Mechanisms of graft rejection :

Hyperacute rejection

• In hyperacute rejection
preformed antibodies react with alloantigens on the vascular endothelium of the graft, activate
complement, and trigger rapid intravascular thrombosis and necrosis of the vessel wall
 9

LO 02

To explain about laboratory

investigation of transplantation
 10

Laboratory investigation of transplantation

HLA typing : Serological Technique

https://www.intechopen.com/chapters/42879

Gold standard

Quicker and cheaper than melacula method

 11

Laboratory investigation of transplantation

HLA typing : Molecular Technique

PCR-sequence specific primer (PCR-SSP)
PCR-sequence specific oligonucleotide probe (PCR-SSOP)
PCR-sequence based typing (PCR-SBT)

https://www.sciencedirect.com/science/article/pii/B9780123694287000306
https://www.researchgate.net/figure/HLA-typing-strategy-The-primer-design-
captures-full-length-HLA-class-I-genes-HLA-A-B_fig1_309596086
 12

Laboratory investigation of transplantation

Cross-match : Cell-base assay

CDC-XM reduced the incidence of

hyperacute rejection

Inability to identify the antigen causing

positive

https://www.intechopen.com/chapters/42879
 13

Laboratory investigation of transplantation

Anti-HLA : Solid-phase assay

https://www.intechopen.com/chapters/42879
https://www.intechopen.com/chapters/42879

Sensitive with high degree of specific to donor antigen, luminescent more sensitive
than ELISA
Capable of quantifying anti-HLA antibodies level
 14

LO 03

To explain about Pathogenesis and of

Signs and symptoms Graft rejection
 15

Direct and Indirect of Graft rejection

https://www.researchgate.net/figure/The-direct-and-indirect-pathways-of-rejection-Recipient-CD4-T-cells-recognize-peptides_fig1_236277505
 16

Pathogenesis and Pathophysiology of Graft rejection

Chronic Rejection

https://flore.unifi.it/retrieve/handle/2158/599069/18128/tesi%20Mariangela%20Sottili.pdf
 17

Pathogenesis and Pathophysiology of Graft rejection

Hyperacute Rejection Acute humoral rejection Thromboembolic event Acute tubular necrosis

Anti-HLA-A32
 18

Signs and symptoms of graft rejection

Fever Fatigue Dyspnea Flu-like systomps

New tissues/ organs The patient will feel There may be pain, swelling in the Symptoms that depend on
will be malfunctioning physically uncomfortable location of new tissue/ organ. the type of new tissue/ organ.
 19

References

Lechler RI, Sykes M, Thomson AW, Turka LA. Organ transplantation: how much of the promise
has been realized Nat Med 2005; 11:605-13.

Hao wang. (2021). Tackling Chronic Kidney Transplant Rejection: Challenges and
Promises. Retrieved November 20,2022, from
https://www.frontiersin.org/articles/10.3389/fimmu.2021.661643/full

Hall BM. Cells mediating allograft rejection. Transplantation 1991; 51:1141-51.

Smadar Eventov-Friedman (2013).Pathways of major histocompatibility complex allorecognition.

Retrieved November 20,2022, from https://www.researchgate.net/figure/The-direct-and-
Indirect-pathways-of-rejection-Recipient-CD4-T-cells-recognize-peptides_fig1_236277505
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Section 3