HLA -Matching in Solid Organ Transplantation

EFI-ASHI-APHIA Summer School 2013 Stintino

16 – 18 September 2013

Carlo Carcassi

•!Still HLA typing?

•!How, when and why?

Changing HLA typing strategies in organ transplantation

IHW! Year! Chair! Venue! Advances!1st! 1964! DB Amos! Durham, USA! Definition of “Hu-1”, “LA” and “Four” antigen specificities!

2nd! 1965! JJ van Rood! Leiden, The Netherlands!

Mixed lymphocyte culture testing!

3rd! 1967! R Ceppellini! Torino, Italy! Family studies; HLA in renal transplantation!

4th! 1970! PI Terasaki! Los Angeles, USA! Definition of 27 HLA-A, B, C specificities!

5th! 1972! J Dausset! Evian, France! Worldwide typing of 49 populations!

6th! 1975! F Kissmeyer-Nielsen! Aarhus, Denmark! Description of Dw specificities!

7th! 1977! WF Bodmer! Oxford, UK! Definition of DR1-7 specificities. HTC testing!

8th! 1980! PI Terasaki! Los Angeles, USA! Definition of MB (DQ) and MT (DR52/53). HLA in transplantation and disease!

9th! 1984! EA Albert/W Mayr! Munich, Germany Vienna, Austria!

New class I and II specificities. HLA class II in renal transplantation!

10th! 1987! B Dupont! Princeton, USA! Establishment of RFLP; T cell clones; HTC methods; Biochemistry – 1D IEF, 2D-gels; Creation of a panel of homozygous cell lines!

11th! 1991! T Sasazuki/K Tsuji/M Aizawa!

Yokohama, Japan! HLA Class II PCR DNA typing; Anthropology!

12th! 1996! D Charron! St Malo/Paris, France!

HLA Class I PCR DNA typing; Anthropology!

13th! 2002! J Hansen! Victoria, Canada Seattle, USA!

Virtual DNA analysis; Identification of SNP markers; Anthropology; Disease association; HSCT!

14th! 2005! J McCluskey! Melbourne,Australia!

MHC and anthropology; Disease; Infection; HSCT; Cancer; KIR; Cytokine genes!

15th! 2008! M Gerbase de Lima/ME Moraes!

Buzios/Rio de Janerio, Brazil!

Anthropology; HSCT; Informatics!

16th! 2012! SGE Marsh/D Middleton! Liverpool, UK! To be determined!

IHW! Year! Chair! Venue! Advances!1st! 1964! DB Amos! Durham, USA! Definition of “Hu-1”, “LA” and “Four” antigen specificities!

2nd! 1965! JJ van Rood! Leiden, The Netherlands!

Mixed lymphocyte culture testing!

3rd! 1967! R Ceppellini! Torino, Italy! Family studies; HLA in renal transplantation!

4th! 1970! PI Terasaki! Los Angeles, USA! Definition of 27 HLA-A, B, C specificities!

5th! 1972! J Dausset! Evian, France! Worldwide typing of 49 populations!

6th! 1975! F Kissmeyer-Nielsen! Aarhus, Denmark! Description of Dw specificities!

7th! 1977! WF Bodmer! Oxford, UK! Definition of DR1-7 specificities. HTC testing!

8th! 1980! PI Terasaki! Los Angeles, USA! Definition of MB (DQ) and MT (DR52/53). HLA in transplantation and disease!

9th! 1984! EA Albert/W Mayr! Munich, Germany Vienna, Austria!

New class I and II specificities. HLA class II in renal transplantation!

10th! 1987! B Dupont! Princeton, USA! Establishment of RFLP; T cell clones; HTC methods; Biochemistry – 1D IEF, 2D-gels; Creation of a panel of homozygous cell lines!

11th! 1991! T Sasazuki/K Tsuji/MAizawa!

Yokohama, Japan! HLA Class II PCR DNA typing; Anthropology!

12th! 1996! D Charron! St Malo/Paris, France!

HLA Class I PCR DNA typing; Anthropology!

13th! 2002! J Hansen! Victoria, Canada Seattle, USA!

Virtual DNA analysis; Identification of SNP markers; Anthropology; Disease association; HSCT!

14th! 2005! J McCluskey! Melbourne,Australia!

MHC and anthropology; Disease; Infection; HSCT; Cancer; KIR; Cytokine genes!

15th! 2008! M Gerbase de Lima/ME Moraes!

Buzios/Rio de Janerio, Brazil!

Anthropology; HSCT; Informatics!

16th! 2012! SGE Marsh/D Middleton! Liverpool, UK! To be determined!

HLA genomic typingRFLP & Southern blotting HLA-DQA1: Reverse dot-blot

SequencingPCR-SSP

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0 5 10 15

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HLA-A,-B,-DR MATCHES

2881 first kidney transplants (1981-2011)

time (years)

0 1 2 3 4 5

tempo (anni)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

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% g

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surv

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p=0.015

HLA-A,-B,-DR MATCHES 488 first heart transplants (1990-2012)

time (years)

HLA-A,-B,-DR MATCHES

0 1 2 3 4 5

tempo (anni)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

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0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

2-5 HLA-A,-B,-DR M (73) 1 HLA-A,-B,-DR M (63) 0 HLA-A,-B,-DR M (40)

p=0.163

176 first lung transplants (1993-2012)

time (years)

0 1 2 3 4 5

tempo (anni)

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0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

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0.4

0.5

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0-2 MM (43) 3-4 MM (450) 5-6 MM (520)

p=0.708

HLA-A,-B,-DR MISMATCHES 1013 first liver transplants (2000-2010)

time (years)

HLA-A,-B,-DR MISMATCHES First liver transplants (2000-2010)

0 1 2 3 4 5

tempo (anni)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

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% g

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surv

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p=0.405 p=0.517

time (years) time (years)

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