Sensitization in Organ Transplantation By: Yadollah Shakiba MD, - - PowerPoint PPT Presentation

By: Yadollah Shakiba MD, PhD

Sensitization in Organ Transplantation

Ba Barrie iers s to suc

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cessf ssful ul tr tran ansp splant ant

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 Immunogenic and polymorphic  Blood groups-ABO  Anti-HLA Antibody  None-HLA Antibody

ABO in Organ Transplant

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ABO selection in highly sensitized patient?

Revolutioni

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zing article ticle

Main Antigens in Allograft Rejection?

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Immune response to polymorphic molecules

Numbers of HLA Alleles HLA Class I Alleles 11,100, 20,182 HLA Class II Alleles 3,920, 7,407 HLA Alleles 15,020, 27,589

The reasons of Anti-HLA antibody production

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 Allograft  Pregnancy  Transfusion  Natural Anti-HLA Ab

HLA Incompatibility Large amount of antigens Long term exposure with immune system Respond to spouse HLA antigens Low amount of leucocytes in blood bags Male without transfusion

Understanding the CRE REG

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Sensitization in Pregnancy or allograft makes many patients incompatible

Understanding the CRE REG

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Sensitization after first kidney transplant in IRAN

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 About 500 patients waiting for second transplant included  Previous transplant was cadaver and living donor  86% of patients were sensitized.  52% were positive for both anti-HLA class I and class II antibodies  3% sera were positive for only anti-HLA class I antibody  31% Sera were only positive for anti-HLA class II antibody  14% sera were negative for both anti-HLA class I and class II

antibodies

 40-50% of women with history of pregnancy are sensitized

Det Detection ection of se sensi sitizing tizing antig tigen en

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Sex/age: F/28 Previous transplant: Negative Blood transfusion: Negative Number of pregnancy: 2

Flow cross match with husband cells

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Anti HLA antibodies detected

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A*23:01- A*24:02- A*25:01- A*32:01 B*13:01- B*27:05- B*38:01- B*44:02 B*49:01- B*51:01- B*52:01- B*57:01

Name Rel. Class I PCR Class II PCR

Patient

Recipient A*02 B*18 C*07- C*12 DQB1*03- DQB1*06 DRB1*03- DRB1*11 DRB3

Name Rel. Class I PCR Class II PCR

Husband

A*02-A*30 B*18-B*49 C*07 DQB1*05- DQB1*06 DRB1*13-DRB1*15 DRB3- DRB5

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CREG Antigens included A1C A1, 3, 11, 19 (29, 30, 31), 36, 80 A2 A2, 9 (23, 24), 28 (68, 69), B17 (57, 58) A10C A10 (25, 26, 34, 66), 32, 33, 43, 74 BW4 A9 (23, 24), 25, 32, B13, 27, 37, 38, 44, 47, 49, 51, 52, 53, 57, 58, 59, 63, 77 B5C B5 (51, 52.) 18, 35, 53 B5C2 B5 (51, 52), 15 (62, 63, 71, 72, 75, 76, 77), 17 (57, 58), 21 (49, 50), 35, 53, 73,78 BW6 B7, 8, 14, 18, 35, 39, 40 (60, 61), 41, 42, 45, 46, 48, 50, 54, 55, 56, 62, 64, 65, 67, 71, 72, 73, 75, 76 B7C B7, 8, 13, 27, 41, 42, 47, 48, 54, 55, 56, 60, 61, 81 B8C B8, 18, 38, 39, 64, 65 B12C B12 (44, 45), 13, 37, 41, 47, 21 (49, 50), 40 60, 61)

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The role of IgM DSA

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This preliminary study implies that pre-formed IgM antibodies may not be harmless autoantibodies and that the presence of IgM DSA should be sought in patients with IgG HLA- or DSA-negative AMR

Our experience with IgM DSA

Anti HLA class I Reactive Antigens IgG High Risk Antigens (MFI >1000) None Moderate Risk Antigens (MFI 500-1000) None Anti HLA class I Reactive Antigens IgM High Risk Antigens (MFI >1000) A*23:01- A*24:02- A*25:01- A*26:01- A*34:01- A*68:01- B*07:02- B*08:01- B*13:01- B*14:02- B*15:01- B*18:01- B*27:05- B*38:01- B:40:01- B*44:02- B*45:01- B*49:01- B*51:01- B*52:01- B*57:01 Moderate Risk Antigens (MFI 500-1000) A*02:01- A*11:01- A*32:01 Anti HLA class II Reactive Antigens IgG High Risk Antigens (MFI >1000)

None

Moderate Risk Antigens (MFI 500-1000)

None

Reactive Antigens High Risk Antigens (MFI >1000) DRB1*01:03- DRB1*04:05 Moderate Risk Antigens (MFI 500-1000) DRB1*10:01- DRB1*16:01- DRB1*04:04- DQB1*04:02- DQB1*03:01- DQB1*03:02

• IgM+++
• IgG3++
• IgG1+
• Complement activation potency:

Underestimation of anti-HLA antibodies

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Annette M Jackson presentation

Role of none HLA antibodies in Rejection

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Annette M Jackson presentation

• 1- HLA matched kidney finally fails
• 2- 15-20% of failed transplants=no

DSA

• 3- hyper acute or acute rejection

despite DSA

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Annette M Jackson presentation

Production of non-HLA antibodies

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Non-HLA antibodies may be present before transplant

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Annette M Jackson presentation

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Diffuse HLA-DR positivity in proximal tubules in active antibody mediated rejection (immunohistochemistry, HLA-DR, 100×).

Indication for non-HLA Ab screening

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 Second transplant patients  Patients with history of hyper acute rejection  Patients with high cPRA  Patients with previous history of hypertension

Major r histocom compatib patibility ility-com comple plex x (M (MHC) ) cl class s I– re rela lated ed ch chain n A (M (MICA) A)

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Patients with anti-MICA antibodies had a 1-year graft-survival rate of 88.3±2.2% as compared with 93.0±0.6% among patients in the MICA antibody–negative group (P=0.01).

N Engl J Med 2007; 357:1293-1300

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Anti ti En Endoth thelial elial antib tibody

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