1. Vojvodić S, Ademović-Sazdanić D.
A case report of KIR haplotype analysis in one family lacking KIR 2DL1-2DP1 genes
Vojvodić S, Ademović-Sazdanić D.
Institute for Blood Transfuson of Vojvodina, Tissue Typing Compartment, Novi Sad, Serbia

2. Klinical importance of KIR genes in HSCT
KIRs are encoded by genes located in the chromosomal region 19q13.4 within the leukocyte receptor complex (LRC). KIR gene cluster exhibits extensive allelic and haplotypic diversity
Belong to non-HLA genes of great importance in HSCT
KIR/HLA missing ligand status is assocated with strong GvL/T effect and therefore with enhanced overall survival, decreased disease relapse, and increased probability of disease-free survival
B KIR haplotypes contribute to relapse protection and improved survival(Cen-B homozygosity )
Imperative in donor search strategy

3. Donor search strategy in our Institute
Since HLA A,B,C,DRB1,DQB1 PCR SSP low resolution genotyping of recipents and related donors
KIR PCR SSP low resolution genotyping
ABO/RHD/RHCE/KKD/MNS low resoution genotyping, CDC-AHG CM, Ab screening/identification by CDC,ELISA
KIR/HLA missmatches
Recipient HLA C1/C1 genotype
Donor A and/or B KIR haplotypes
Donor KIR B group content (IPD-KIR Database)
In we started with PCR SSOP HLA/KIR low resolution typing (Luminex) –unrelated HSCT donors

4. KIR/HLA missmatches INHIBITORY KIR KIR LIGAND KIR2DL1
HLA-C group 2 (02, 04, 05, 06, 15, 1602, 17,18)
KIR2DL2/3
HLA-C group 1 (01, 03, 07, 08, 12, 13, 14,1601/4)
KIR3DL1
HLABw4
(B*27,A*23,A*24,A*25,A*32)
KIR3DL2
HLA A*03,A*11
DONOR
RECIPIENT
Farag S. S. et al. Blood 2002; 100:

5. KIR A and B haplotypes KIR GENES HAPLOTYPE A HAPLOTYPE B KIR2DL1
“FRAMEWORK“GENES
HAPLOTYPE B
KIR2DL1
KIR2DL3
KIR2DS4
KIR3DL1
KIR2DL4
KIR3DL2
KIR3DL3
KIR3DP1
KIR2DS1/2/3/5
KIR3DS1
KIR2DL5 (A/B)
KIR2DL2

6. Group A and B KIR haplotypes centromeric (Cen) and telomeric (Tel) gene-content motifs
KIR3DL3-KIR2DL3-KIR2DP1-KIR2DL1-KIR3DP1
Cen-B1
KIR3DL3-KIR2DS2-KIR2DL2-KIR2DL5B-KIR2DS3 (or KIR2DS5)- KIR2DP1-KIR2DL1-KIR3DP1
Cen-B2
KIR3DL3-KIR2DS2-KIR2DL2-KIR3DP1
Tel-A1
KIR2DL4-KIR3DL1-KIR2DS4-KIR3DL2
Tel-B1
KIR2DL4-KIR3DS1-KIR2DL5A-KIR2DS3
(or KIR2DS5)-KIR2DS1-KIR3DL2
Hou L. et al. Genes and Immunity 2012;13:47-58

7. KIR and HLA alleles i parents
Mother(M.Z.):
KIR: 2DL2; 2DL4(norm and del); 2DS2;
2DS4(del-22bp);3DL1;3DL2;3DL3;3DP1
HLA:A*24,*32; B*08,*27; C*02,*07;
DRB1*03,*16; DQB1*02,05;
 Father (M.A.):
KIR: 2DL2;2DL4(norm);2DL5;2DS1;2DS2;
2DS5;3DL2;3DL3;3DS1;3DP1
HLA:A*02,*32; B*27,*41; C*02,*07;
DRB1*03,*16; DQB1*02,*05;

8. KIR and HLA alleles in offsprings
 Patient (M.M.):
KIR:
2DL2; 2DL4(del); 2DL5; 2DS1; 2DS2;2DS4(del-22bp); 2DS5; 3DL1;3DL2;3DL3;3DP1
HLA:
A*02,*32;
B*27,*41;
C*02,*07;
DRB1*03,*16;
DQB1*02,*05;
Brother(M.M):
KIR: 2DL2;2DL4(del);2DL5;2DS1;
2DS2;2DS4(del-22bp); 2DS5;
3DL1;3DL2;3DL3;3DP1
HLA:A*02,*24; B*08,*41; C*07,-;
DRB1*03,-; DQB1*02,-;
Brother(M.Z.):
2DS2;2DS4(del-22bp), 2DS5;
3DL1; 3DL2;3DL3;3DP1
Ludajić K. at al. Bone Marrow Transplantation 2009; 44: 97–103.

9. HLA haplotypes segregation analysis

10. KIR haplotypes segregation analysis

11. KIR 3DS1 segregate as 3DL1
3DL1*009 is formed by conversion between 3DL1*001 and 3DS1*01301

12. KIR genotypes frequencies
Father (M.A.):
CenB2/CenB2 and TelB1/TelB1 with frequency of 0,5-2,9%
Mother (M.Z.):
CenB2/CenB2 and TelA1/TelA1 with frequency of 0,5-6%
Offsprings:
CenB2/CenB2 and TelA1/TelB1 with frequency of 0,5-1%

13. KIR 2DP1 and 2DL1 allele frequencies
-Belgium 87%
-Bulgaria, England, Germany 91%
-Czech Republic 95%
-Finland 100%
-France 97%
-Greece 89%
-Iran 99%
-Italy 95%
2DP1
-Belgium 99%
-England 96-99%
-Czech Republic 94%
-France 98%
-Portugal 89%
-Iran 96%
-Italy 96,9%

14. Conclusion
KIR and HLA analysis of presented family was interesting for a several reasons:
1) presence of rare KIR genotype with KIR 2DP1-2DL1 absence in both of parents and one mutualy shared haplotype (Cen-B2),
2) presence of probably hybrid KIR haplotype in offsprings and also rare KIR genotype with absence of KIR 2DP1-2DL1 genes
3) HLA identity between the father and the daughter, “best” B KIR gene content,1 KIR/HLA MM(3DL2)