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On this page we will try to explain some behaviour of the match engines in our Search and Match application.


Antigen Recognition Domain explained

  • The antigen recognition domain (ARD) is the binding groove of the HLA peptide. This is the region interacting with the presented antigen and T-cell receptor.
  • All alleles that express the same amino acid sequence in this region are considered an allele match.
  • The ARD is encoded on:
    • exon 2 & 3 for HLA class I
    • exon 2 for HLA class II

1. Null allele treatment in Hap-E search

  • Null alleles are treated as absent, i.e. the second typing matches as homozygous.
  • Null allele matching rules are applied to:
    • All high resolution null alleles.
    • Null alleles as part of multi allele codes if the null allele is part of a haplotype matching the donor‘s (patient‘s) HLA typing.
  • Null allele matching rules are only applied to one typing of the locus.

The following table explains situations where Hap-E performs null allele treatment and whether this is a considered a (potential) match or not.  

Patient typing

Donor typing

Hap-E

ATLAS

A*03:01,

A*01:11N

A*03:01, A*03:01

matches

matches

A*03:01, A*01:11N

A*03:01, A*02:125N

matches

matches





If there is a haplotype compatible with the donor typing containing A*02:125N then




A*03:01, A*01:11N

A*03:01, A*02:GFJM

matches

matches

A*03:01,

A*03:01

A*03:01, A*02:XX

matches

matches




A*03:01,

A*03:01

A*03:01,

A*01:01:01G

does not match

does not match





A*01:11N,

A*02:125N

A*03:01,

A*03:01

does not match

does not match

02:GFJM ≜ 02:01/02:105/02:125N


2. Search with two mismatches

Hap-E search

ATLAS search
The two mismatches can be on any locus.

The two mismatches can be on any locus.


3. Donors with DNA and serologic typing

Hap-E search

ATLAS search

Only the DNA typing information is used for matching.

Only the DNA typing information is used for matching.

4. Returning donors without typing at DRB1

Hap-E search

ATLAS search

Yes, when default 'return only donors with typing at DRB1' filter has been switched off and donor does have typing at A+B+C and/or DQB1 loci.

No, because donor without typing at DRB1 are not accepted by ATLAS as valid donors.


5. Match grades: Overview

Standard match grades

DPB1-specific match grades

Applied to locus A, B, C, DRB1, DQB1

Applied to DPB1 only. Uses TCE3 model. 




6. Handling of HLA*DRB3, DRB4, DRB5, DQA1 and other loci not considered for overall match probability

Hap-E search

ATLAS search

HLA*DRB3/4/5, DPA1, DQA1 and E are validated and shown in the full report, including information whether they are matched or not.

Loci other than A, B, C, DRB1, DQB1 and DPB1 are not validated or imported by ATLAS and therefore also not returned. 


7. Handling of 'NEW' alleles

Handling of new alleles that do not have an official name yet.
For guidelines regarding implementation and reporting of 'NEW' alleles, please read https://onlinelibrary.wiley.com/doi/10.1111/tan.15048

Hap-E search

ATLAS search

Supported for Donors and Patients. However, Search & Match including Dataupload currently only supports NEW alleles for Patients. Therefore only NEW alleles for patients will be processed in Search & Match.

Currently not supported.
Functionality will be added in the future.

8. Cord Blood search options

Hap-E search

ATLAS search

Allele matched:

  • n/10, n/8 and n/6 search
  • Up to 4 mismatches

Allele matched:

  • n/10, n/8 and n/6 search
  • Up to 4 mismatches
  • n/6 search at HLA-A, B, DRB1
  • n/6 search at HLA-A, B, DRB1 - class I matched at antigen level and class II matched at ARD level
  • n/6 search at HLA-A, B, DRB1


9. Probability display

Hap-E search

ATLAS search

All probabilities are rounded to integer values.

→ 0%:

  • Values 0 < p < 0.5
  • No shared genotype between donor and patient.

All probabilities are rounded to integer values.

→ 0%:

  • Values 0 < p < 0.5
  • No shared genotype between donor and patient.


10.1 Locus match probabilities: Definition

Hap-E search

ATLAS search

match, i.e. 10/10, 8/8 or 6/6

  • The locus match probability is the relative probability that this locus is a match in the 1 mismatch case.

mismatch, i.e. 9/10, 7/8 or 5/6

  • The locus match probability is the relative probability that this locus is a match in the 2 mismatch case.

So this probability provides information on which locus the next mismatch will occur.

match, i.e. 10/10, 8/8 or 6/6

  • The locus match probability is the probability that this locus is a match no matter the amount of overall mismatches.

mismatch, i.e. 9/10, 7/8 or 5/6

  • The locus match probability is the probability that this locus is a match no matter the amount of overall mismatches.

So this probability provides information on the probability that this locus will be a match.


10.2 Locus match probabilities in search: Not displayed

In some cases the value is not defined and no locus match probability is displayed:

Hap-E search

ATLAS search

match

  • When p1 = 0 (division by zero, not defined).

mismatch

  • When p2 = 0 (division by zero, not defined).
  • When a donor/CBU already has at least two known mismatches. As Hap-E only calculates match probabilities for up to 2 mismatches, Hap-E also is not able to calculate the locus-specific match probabilities in case of the third mismatch.

inexplicable donors

  • When a donor's phenotype cannot be explained by the haplotype frequency sets used for probabilistic matching. It is therefore impossible to calculate match probabilities both at the considered loci in total and per-locus. 

match

  • Locus probabilities will always be displayed for explicable donors.

mismatch

  • Locus probabilities will always be displayed for explicable donors.


inexplicable donors

  • When a donor's phenotype cannot be explained by the haplotype frequency sets used for probabilistic matching. It is therefore impossible to calculate match probabilities both at the considered loci in total and per-locus.


10.3 Locus match probabilities in Hap-E and ATLAS search

Example 1: Hap-E


Example 2: Hap-E


Example 3: Hap-E


Example 4: Hap-E


Example 1: ATLAS


Example 2: ATLAS


Example 3: ATLAS


Example 4: ATLAS


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