Lab Medicine Rounds

In this episode of Lab Medicine Rounds, as we head into the holiday season, Justin Kreuter, M.D., and Andrés Jaramillo, Ph.D., Associate Professor of Laboratory Medicine and Pathology at Mayo Clinic and director of the Histocompatibility Laboratory at Mayo Clinic’s Arizona campus, discuss the ultimate gift of organ transplantation.

Show Notes

Timestamps:

00:00 Intro

01:05 How did you first get interested in supporting organ transplantation? 

04:53 What are the organs that we can transplant?

06:00 When we are at the Department of Motor Vehicles, we can register as a donor and make our wishes known to our family, is that right?

07:03 If people are interesting in donating a kidney, for example, do they reach out to their local hospital and let them know they are interested in being a donor?

08:50 How does your work in the Histocompatability laboratory, how does it support transplantation? 

10:57 Can you give our audience kind of a flavor of how does this work to do this kind of dance to match donor and recipient and have a successful transplant? 

13:11 What’s on the horizon for HLA and histocompatibility in the next couple of years?

18:30 The ability for us to identify a patient, these patients who could not get a transplant are now able to get the transplant because of these improvements in the laboratory.

20:01 Outro


Resources: 
 
Successful pig to human transplant articles:

What is Lab Medicine Rounds?

A Mayo Clinic podcast for laboratory professionals, physicians, and students, hosted by Justin Kreuter, M.D., assistant professor of laboratory medicine and pathology at Mayo Clinic, featuring educational topics and insightful takeaways to apply in your practice.

(upbeat music)

- This is Lab Medicine Rounds,

a curated podcast for physicians,

laboratory professionals and students.

I'm your host, Justin Kreuter,

the bow tie band and a
blood transfusion medicine

pathologist at Mayo Clinic.

As the temperatures turn cooler,

and we've gotten some
snow here in Minnesota,

we decided to travel south

and connect with some of our colleagues

at the other Mayo Clinic campuses
over these winter months.

Today, we're rounding with Dr. Jaramillo,

an associate professor

of laboratory medicine and
pathology at Mayo Clinic

and director of the
Histocompatibility Laboratory

at Mayo clinic, Arizona.

As we head into this holiday season,

we think it's really
appropriate that we're fit

putting focus on the ultimate
gift, organ transplantation.

Thanks for joining us today to discuss

this very important topic, Dr. Jaramillo.

- Thanks Justin for the invitation.

I'm really excited to be here.

- What's your origin story?

How did you first get
interested in the ultimate gift?

How did you first get
interested in supporting

organ transplantation?

- Well, it's a long story,

but I'm gonna make it
as short as possible.

Of course, we have only 20 minutes,

but in college I always
wanted to go to medical school

and then I was quite
interested in immunology.

And I remember that the HLA
class, it was fascinating.

I thought it was the most
fascinating class I ever had

and because the HLA system is actually

the most complex system that
we have in the genetic systems

of the human genome,
'cause it has right now

32,000 different variants.

So I thought it was just amazing that,

and HLA, obviously a for
the immunology class,

it was told, the class is
told to transplantation,

not really

for the function of the HLA system.

So anyway, he happens that in the 1980s,

my brother was diagnosed
with a kidney disease.

I mean, we knew that his kidneys
were gonna eventually fail

and the kidney did, his kidneys did.

So, he needed a kidney transplant in 2001.

So, actually I was actually
believe it or not quite excited

to kind of have these opportunity

to give my brother a kidney.

So we are five siblings
and it happens that,

that was the only one
that was not completely

genetically compatible.

So my little sister gave him a kidney.

And I always talk, as you
say, this was such a gift.

I gift of love, but also
the gift of science.

I mean, these are true miracle.

'Cause we have this
person that is close to me

that 20 years ago, he got
an organ for my sister

and he live a wonderful life.

I mean, he's a retired
lawyer now he's still,

I mean, that was to me, was amazing.

And I always, all these years I felt

that I kinda missed
out in somehow in being

part of that thing.

So, of giving him my own kidney.

So, I always thought that
it was just fascinating.

That's my a very personally
story that I have.

- Yeah, I love that very
personal connection to this.

And also I love that
it highlights the fact

that this is really one of these places

where the basic science
research really informs

the clinical practice
in a very direct way.

- Correct.

Yeah, and so that
actually that gear me out

actually of medical school.

I was going to medical
school and I switched

to basic science to get my PhD

because I really wanted to focus

on the transplantation
part of medicine, really.

I mean, more direct involvement
in the genetic analysis.

And I felt that I could
help the patients more,

more directly, even though
it sounds kind of weird

because I don't see in, but I feel

that I could do a better
job in the lab doing that.

- So maybe for,

we've got a very diverse
audience on this podcast.

We've got physicians, we've
got laboratory professionals.

We've got students that listen to this,

maybe can you kinda give us a
flavor for what are the organs

that we actually can transplant?

- Yeah, well, there are the
two types of donors, of course,

the deceased donors.

You can actually get a heart, of course

from a deceased donor,
but from live donors,

live donors can't donate
bone marrow of course.

You can donate one of your kidneys,

a one full lung or part of your lung,

part of the liver of course,

and part of the pancreas
and part of the intestines

generally a healthy person can donate

literally six organs.

If we count bone marrow
as an organ as well.

So it is a long list

of organs and donors can live
a healthy life after that.

- So, I guess for people that
are interested in potentially

becoming a donor, or giving this gift,

I guess, for a deceased
donation it seems like

when we are at the
department of motor vehicle

we can register as a donor.

Is that right?

And then make our wishes
known to our family?

- Correct, yeah.

Yeah, it does pretty much
the best way of doing it.

So, you are actually are in the system

or otherwise at the time of your eventual

death by an accident, there
may be some emotional issues

when the family, when
somebody ask in the hospital

to the families, hey,
there is a possibility

that your loved one can be an organ donor.

However, you are approaching the family

in a very, probably the
worst time of their lives.

That is very tough for them
to make a rational decision

at that moment.

So yeah, the best way is
to just have your wishes

kind of registered in your license.

Yeah.
- I see.

And then if people are
interested in donating,

let's say a kidney or
something, for example,

is that just reach out
to their local hospital

and let them know that they're
interested in being a donor.

- Correct, yeah.

Most live donors, there are
about 6,000 live donations

in the United States every
year, last year, for example.

But of course from a family member

to a family member member,

but many people use, feel that the need

to donate a kidney

or easily, there are many,
many people that register

as bone marrow donors.

But yeah, if you feel
that you want to donate,

it's usually a kidney, of course,

'cause it's the kind of the easiest,

the less risky organ to give,

people usually come to
the hospital and say,

I wanna be a donor.

I wanna donate my kidney.

I'm healthy.

I wanna give this, have
this gift to somebody

that will need a kidney
otherwise that person

will continue to have a pretty
horrible life on dialysis.

And dialysis is not a
healthy way to leave.

I mean, these people that
do have the conventions,

they come in to do it.

- So, we'll put a couple
of links down there

for those that are listening,

helpful links to kind of get in touch.

If you're more interested
in more information,

I'll put links to National
Marrow Donor Program

and that kind of information.

Dr. Jaramillo, how does your work

in the Histocompatibility
Laboratory, in the broad stroke,

how does it support transplantation?

- Yeah, we actually,
the HLA Lab is actually,

even though we do complex analysis,

it's actually quite simple.

We really literally do two things.

We do an initial genetic
analysis or the HLA system,

the geodetic system of 11 genes.

And it used to have a kind
of an initial assessment

of the genetic matching
between the recipient

and the potential donors.

And that's kind of a
minor risk assessment.

I mean, if you happen to have a good match

with the kidney donor, that's great.

If you don't, it's not a contraindication

to transplantation, but
your risk assessment

on having a rejection down
the road is a little higher

just as, very, very low.

Then, the most important
thing is that we do

an immunological analysis
of your antibody profile.

And that is really kind of
when the matching happens.

'Cause if you have an antibody
present against the donor,

then you will have a
rejection of that organ.

So, we make sure that
if you have antibodies,

we avoid those antibodies
and to pick a donor

for which that patient
doesn't have any antibodies

and guaranteed that, that
organ is gonna last several

and several years.

So it that's literally what we do.

- I see.

And I imagine that (chuckles)

it sounds like you're
probably not giving yourself

enough credit.

Yes, you see talk about
more than 32,000 genes,

but it sounds like
you're really interacting

with a number of different physicians,

nurses from different specialties.

Could you kinda give our
audience kind of a flavor

of how does this work
to do this kind of dance

to match donor and recipient

and have a successful transplant?

- Well, for live donors,

we do have time

to type the entire families

and then we can actually pick and choose

in a timely manner the
best donor for that patient

based first on the antibody profiles.

And then

if your siblings are a
full match, that's perfect.

For deceased donors, we need to do this

in a very, very fast way.

So, we actually type the
donors in what we call a stat,

we turn three hours and
then by a computer analysis,

because it's almost
impossible to do it by hand,

we do the antibody profile
against the genetic profile

of the donor to try to find out

what is the best at this point,

if it is a disease
donor, we try to find out

who has the best recipient for that donor

and not the other way around.

So, a recipient that
doesn't have antibodies

against that donor.

So, that's basically what we do.

So, it's basically a genetic profile

against antibody profile of the recipient

and we just try to find kind of the best

holes in the antibody
profile of the recipient.

- Wow!

It strikes me too that as
managing this and getting it right

and getting it as best as possible,

and there's all kinds
of ethical challenges

to navigate as well.

I'm kind of curious, what's your thoughts

for what's on the horizon
for HLA in histocompatibility

in the next couple of years you think?

- There has been a very rapid developments

in the molecular assays that we do.

And this has been happening
in the last two, three years,

that we are getting
right now slowly getting

into all the HLA labs in
the country and in the world

better testing, molecular
testing for the genetic analysis

that we do with the donors.

So, that is happening right now

and also we are getting
better kind of what they call

high resolution testing of
the antibody profile as well.

So, we can actually, I
think we are getting better

and better in hiring a
better profile analysis

of the genes that the donors have

and/or the antibodies
that the patients have.

So we can actually have
kind of a better assessment,

risk assessment.

And the other way we
can actually get organs

to patients that are highly sensitized,

meaning that they have a very
wide profile of antibodies.

We can actually, with these
new tools find these people

the right donor, the right organ.

And that is internally what
is happening in the HLA.

In transplantation though, I think

the field of xenotransplantation is been,

that concept has been around forever.

So, is basically xenotransplantation

is transplantation from a non-human,

from another species.

And actually the best
species to get organs from

is the pig.

'Cause the pig actually

you can have some breeds
of pigs that are in between

120 pounds to 200 pounds.

So, their physiology is
very similar to humans.

They have the pretty much the
air in the size of the organs

are quite similar.

So, if you have a patient
that he weighs 180 pounds,

you can find a pig that weighs 180 pounds.

The kidneys, the heart, the
livers are gonna be basically

exactly the same size.

So it's perfect for that patient,

but only until now, I mean,
last year in John Hopkins,

there was really the first pig to human

experimental transplant.

And it was successful
because this is a genetically

modified pig where they actually were able

to reduce the expression of
what, of the HLA of the pig,

which is called SLA
swine leukocyte antigen.

In humans is human leukocyte antigen.

In pigs is swine.

This is called SLA.

They were able to attain this
kidney in an experimental

brain dead patients for several days.

So, that was really, really exciting.

That is not gonna have replace,

it is not gonna get us out of business,

but we'll give an organ to these patients

that I have mentioned before,

they have a very large
profile of antibodies

for which is basically
impossible to find them

a good human donor in the donor pool.

- So, when I hear you saying,

correct me if I'm misunderstanding.

Is that the xenotransplantation
you see as like,

really a bridge to get us a
little further down the road

to when we might find the
definitive transplant.

- It could be a temporary bridge here

until, or depending on how good

the genetic manipulation of the pig.

It could be forever.

It could be a permanent organ
that, that person can have,

otherwise that person would have

to find a human donor for.

I personally was really excited about it

because I remember
writing papers about these

back in the '90s.

And he was like, oh,
he's gonna happen next.

And it never happened
because it's so complex.

So now, it really happened.

- That's wonderful.

And then I guess the other
part you were talking about

what's happening in the laboratory about

getting better molecular assay's,

getting a better antibody profile.

You were highlighting that
then it's gonna be the ability

for us to identify a patient
that's highly aluminized

that has lots of antibodies.

These patients who used to not
be able to get a transplant,

you're saying is now
getting the transplant

'cause there these
improvements in the laboratory?

- Yes, correct.

Yeah, he's basically trying
to have a very small hole

that we couldn't see
before, like a small window.

So if you don't have any antibodies there,

the window is as big as a door.

If you have a lot of antibodies,

you literally have no window.

So, now with these new
tests, we can actually find

small windows to that possibility.

And that is very exciting.

We are actually seeing
that now in the practice

that we are able to
transplant these people

that have been waiting
for a kidney for 10 years,

but now that we can actually do it,

we can actually find them a donor.

So that is, and the
taste is getting better,

not necessarily better in
resolution, but faster.

So that's the thing that
we can actually type

a deceased donor in hydro solution

in a timely way and then do it.

- That's wonderful.

I think, my sense is people

that are on the donor waiting list,

things that are happening faster,

exciting developments
that have (chuckles).

- Yes, of course.

- So, thank you so much.

We've been rounding with Dr. Jaramillo

talking about the ultimate
gift of organ transplantation.

Again, in the show notes,
we're gonna have some links

to some of the organ
transplant organizations

here in the United States.

And we'll also have a link to
that paper from Johns Hopkins

that Dr. Jaramillo mentioned for us.

Thank you so much, Dr. Jaramillo.

- Terrific.

- To all of our listeners,
thank you for joining us today.

We invite you to share your thoughts

and suggestions by email.

Please direct any suggestions
to mcleducation@mayo.edu.

If you've enjoyed Lab
Medicine Rounds Podcast,

please follow or subscribe.

And until our next rounds together,

we encourage you to continue
to connect lab medicine

and the clinical practice
through insightful conversations.

(upbeat music)