Using HLAMatchMaker:Using HLAMatchMaker: Maternal-Fetal Incompatibility and Maternal-Fetal Incompatibility and

the Risk of Diseasethe Risk of Disease

Miguel Angel GonzalezMiguel Angel Gonzalez

Mentor: Janet Sinsheimer, UCLAMentor: Janet Sinsheimer, UCLA

Hsinju Hsieh, UCLAHsinju Hsieh, UCLA

OutlineOutline

IntroductionIntroduction

HLAMatchMakerHLAMatchMaker

ResultsResults

ConclusionsConclusions

HLA IncompatibilityHLA Incompatibility

Human Leukocyte AntigenHuman Leukocyte AntigenPresence of structures on cells that are sites Presence of structures on cells that are sites

for antibody bindingfor antibody binding

ProblemsProblemsMother and fetus closely matchedMother and fetus closely matched

Fetus does not set up correct immunological Fetus does not set up correct immunological barrierbarrier

Experimental DataExperimental Data

Family StudiesFamily StudiesMother, father, and at least 1 child with Mother, father, and at least 1 child with

schizophreniaschizophreniaHLA-A, B, & DRB1 types were determined HLA-A, B, & DRB1 types were determined Study focuses on mother-fetus relationshipStudy focuses on mother-fetus relationship

Current StudiesCurrent Studies WHOWHO Current method Current method

for HLA comparisonfor HLA comparison

Biological Biological comparison using comparison using serum screeningserum screening

Match = 1Match = 1 Mismatch = 0Mismatch = 0

Chris O’Callaghan – University of Oxfordhttp://neelix.molbiol.ox.ac.uk:8080/userweb/cocallag/

HypothesisHypothesis

Incompatibility between the mother and Incompatibility between the mother and fetus with respect to HLA can be a risk fetus with respect to HLA can be a risk factor for neurological diseases such as factor for neurological diseases such as schizophrenia.schizophrenia.

Also, to quantify the level of mismatching Also, to quantify the level of mismatching and to determine how sensible the WHO and to determine how sensible the WHO method is.method is.

HLAMatchMakerHLAMatchMaker

Written by Rene J. Duquesnoy, Ph.D.Written by Rene J. Duquesnoy, Ph.D.

Computer algorithm for identifying Computer algorithm for identifying acceptable HLA mismatches for patients acceptable HLA mismatches for patients without the need for extensive serum without the need for extensive serum screening screening

HLAMatchMakerHLAMatchMaker

Purpose: to identify the best candidates for Purpose: to identify the best candidates for organ transplantationorgan transplantation

Compares the Compares the

amino acid amino acid

sequences of sequences of

HLA antigens.HLA antigens.

Internship GoalInternship Goal

To adapt HLAMatchMaker to the studies of the To adapt HLAMatchMaker to the studies of the Sinsheimer lab.Sinsheimer lab.

Use HLAMatchMaker to identify differences in Use HLAMatchMaker to identify differences in the amino acid sequences of mother and fetus the amino acid sequences of mother and fetus HLA.HLA.

Compare to the current analysis: Compare to the current analysis: WHO vs HLAMatchMakerWHO vs HLAMatchMaker

To determine mismatch severityTo determine mismatch severity

HLAMatchMaker ResultsHLAMatchMaker Results

HVG Compatibility #mmDonor

Donor types as Trp(9-199) Mismatched Trps in Positions 9-199

A*0201 0 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

A*2301 9 9S, , , , , , , ,62Ee,66GKv, ,74D,76En,80rIa,82aLr, , , , , , , , , , ,151aRv, , , ,166Dg, , , , , , ,

B*1501 0 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

B*4901 6 9H, , , ,41T,45Ke, , , , , , ,76En,80rIa,82aLr, , , , , , , , , , , , , , , , , , , , , ,

A*02

A*23

B*15 B*49

A*02

A*02

B*15

B*15

Child Mother

Visual ComparisonVisual Comparison

A*23 9S 62Ee 66GKv 74D 76En 80rIa 82aLr

A*02 9F 62Ge 66rKv 74H 76Vd 80gTl 82lRg

A*02

A*23

166Ew151aHv149aAh144tKh142T107W

166Dg151aRv149aAr144tQr142I107G

HLAMatchMaker WHO ComparisonHLAMatchMaker WHO Comparison

Using an excel macro (efficient), large sets Using an excel macro (efficient), large sets of data can be analyzed.of data can be analyzed.

To make comparable to WHO, To make comparable to WHO,

Match = 1Match = 1

Mismatch = 0Mismatch = 0

Results used to construct a comparison Results used to construct a comparison table (Pivot Table).table (Pivot Table).

Pivot TablePivot Table

Count of mmHLA-ACount of mmHLA-A match_amatch_a   (WHO)(WHO)      

mmHLA-AmmHLA-A 00 11 Grand TotalGrand Total

00 158158       158158

11    8383 8383

     

Grand TotalGrand Total 158158 8383    241241

HLAMatchMaker

ConclusionConclusion

Goal AchievedGoal AchievedUsing excel macros it was possible to adapt Using excel macros it was possible to adapt

HLAMatchMaker to the Sinsheimer lab HLAMatchMaker to the Sinsheimer lab studies.studies.

Results showed no difference between Results showed no difference between WHO and HLAMatchMakerWHO and HLAMatchMaker

HLAMatchMaker results can be used to HLAMatchMaker results can be used to support WHO findingssupport WHO findings

Future StudiesFuture Studies

Determine the severity of mismatchingDetermine the severity of mismatchingDifferences in amino acidsDifferences in amino acids

AcknowledgementsAcknowledgements

Dr. Janet Sinsheimer, UCLADr. Janet Sinsheimer, UCLADr. Christina Palmer, UCLADr. Christina Palmer, UCLAHsinju Hsieh, UCLAHsinju Hsieh, UCLA

FundingFundingNIHNIHNIMHNIMHSoCalBSISoCalBSI