hla und stammzelltransplantation - rotes kreuz · 2010-03-10 · hla und stammzelltransplantation...
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HLA und Stammzelltransplantation
31. Informationsgespräch der Blutspendezentrale für Wien,
Niederösterreich und Burgenland
Issues
• Humanes Leukozyten Antigen-System– Struktur & Zellbiologie– Polymorphismus &
Peptide– Alloreaktion (TCR,
KIR)– Typisierung
• Stammzelltransplantation– Spender-Auswahl– Unintelligent Mismatch– Intelligent Mismatch– HLA ist viel, und doch
nicht alles
Proteasome
Cytosol ER
TA
P
Cell membrane
ER MIIC
Cell membrane
DMDO
Systematik-Allele (n)
• Klasse I– Klassisch
• HLA-A 617
• HLA-B 960
• HLA-C 335
– nicht-klassisch
• HLA-E 9
• HLA-F 21
• HLA-G 28
– post-modern
• MICA 61
• MICB 30
• Klasse II
– Klassisch
• DRB1 542
• DQB1 87
• DPB1 127
– nicht-klassisch
• DMA 4
• DMB 7
• TAP1 7
• TAP2 4
HLA-Gene - Chromosom 6p21
B C ADP DQ DR
127 x 87 x 542 x 960x335 x 617
= 1,18 x 1015
Klasse II K l a s s e I
Anzahl der Allele:
TCRα, ß
HLA h.c.ß2 MGPeptide
allo
allo
alloallo
KIR-HLA vs. TCR-HLA
KIR2DL2
KIR2DL2
KIR2DL2
KIR2DL2
KIR2DL2
KIR2DL2
The Size Problem
Immunoglobulin
HLA
Donor Selection
Type Patient
Type Donor
Crossmatch
Interpretation
Blood Groups (easy)
Type Patient
Type Donor
Crossmatch
Interpretation
A
A
...
�
A
0
...
�
A
B
⌧
⌧
HLA (complicated)
Type Patient
Type Donor
How should we go on?
Interpretation
HLA-A2, B8, DRB1*0301
HLA-A*0201, B*0801, Cw*0701, DRB1*0301, DRB3*0101, DQB1*0201
?
�⌧
HLA (complicated, because)
Loci?
Resolution?
Match?
Technique?
Low resolution ... 2 digits A*02High resolution ... 4 digits A*0201
A, B, C, DRB1, DRB3/4/5, DQB1, DP
A mismatch is a mismatch is a ...
How many positions identified?
Cumulative incidence estimates of grades III-IV acute GVHD according to recipient disparityPetersdorf et al., Blood 1998
Mismatch
Time
Petersdorf et al. (Blood 2004; 104: 2976)
cGVHD
Greinix et al. (Bone Marrow Transplantation 2005; 35: 57)
Survival
Greinix et al. (Bone Marrow Transplantation 2005; 35: 57)
Intelligent Mismatch
Kärre, Science 295, 2002, 2029 - 2031
Relapse and KIR-Ligand Differences
Beelen et al. (Blood 2005; 105: 2594)
NOD2/CARD15
• an intracellular sensor to muramyl dipeptide
• mediating consecutive nuclear factor B (NF-B) activation4
• expression restricted to intestinal epithelial cells (IECs) and cells of monocyte-macrophage lineage
Holler et al., Blood 104:889 (2004)
NOD2/CARD15