I'll introduce the next speaker, my long-standing
colleague at Johns Hopkins and friend, Felipe Andrade who is
an expert in autoimmune disease at Hopkins.
He'll be talking about Sore Joints and Bad Breath,
What is Going on?
Felipe?
>> [INAUDIBLE] Can I
can use this one?
>> Sure.
>> Yeah, this is easier for me to see the slides.
Okay, good morning everybody, thanks so much for being here.
And the division of Methodology at Hopkins is
focused on understanding the cause of and
the specific group of auto immune diseases.
And today I'm going to talk about my work on this area.
So this way, this way, okay.
How can I move it forward?
Whoops, it wasn't me, okay.
Thank you.
So the function of the immune system is to protect against
environmental factors, such as bacteria, virus.
Also against malignant tumors.
And some of this function is,
oops, is driven by the production of antibodies.
So the antibodies have proteins that
recognize the foreign invaders, the bacteria, the viruses.
And they help the clearance of these pathogens.
And then the antibodies stay to give a second protection
if the individual is exposed again to the same pathogen.
In autoimmune diseases,
antibodies are made against normal proteins of the body.
So these antibodies can reduce damage and
destruction of the different organs in the body.
So autoimmune diseases can have different phenotypes,
depending on the antibody that is made and
depending on the organs that are being damaged.
So today I'm going to talk about my work on rheumatoid arthritis.
This is a disease that affects the joints.
It causes inflammation and destruction of the joints.
It is present in about 1% of the general population.
About 1.3 million Americans are affected by this disease
which can be very debilitating and
also associated with high mortality.
So autoimmune diseases are the consequence
of the interaction of different factors.
You need to have a genetic susceptibility, some defect in
the immune system, and also something in the environment.
These are complex diseases,
which they need to have all three components to be present.
So by modifying at least one of these, it might be possible to
prevent the disease or even to cure the disease.
Although there are major advances in genetics and
also in the way to the immune system.
Environmental factors are still a major site in which we can
intervene and modify and prevent disease.
Something that is interesting is observation that it appears
existing and maybe the disease was introduced from America.
This idea has brought the hypothesis that maybe
the disease has been driven by a pathogen.
Some interesting observations,
which are observations from the late 1800s and early 1900s.
Is the association between rheumatoid arthritis and
periodontal disease.
Periodontic disease, a chronic inflammatory process of
the gums, which are driven by bacteria.
And they have [INAUDIBLE] diseases, not only [INAUDIBLE].
There is about.
More on that, 1000 bacteria,
different bacteria that are in the mouth.
Some bacteria are good.
Some bacteria are bad.
And identifying those that
are arthritis has been a big challenge.
Something that is a unique feature in and
in fact is part of the.
Is they find in the patients have antibodies against proteins
that are citrullinated.
So in normal conditions,
proteins can diversify their function by being modified.
These modifications look a costume, as are shown here,
in which a single protein can make different functions by
adding something, here represented by hats.
Or a mustache or glasses.
So when you add this little modification a protein can
have different functions.
And one of these modifications that is called citrullination
is a target for
the antibodies in patients with rheumatoid arthritis.
So a part of a major focus on my
lab is to understand what drives this process of citrullination.
That is important for
the activation of the new response [INAUDIBLE].
So if you analyze the joint of a patient,
something that is striking is that all this black here but
you can see are proteins are.
If you compare with the second lane in which we have a sample
from a patient that doesn't have rheumatoid arthritis or have
a different disease, you don't see all these black components.
In fact, from now everything that you
see that is black means striation.
When we analyze the gums of patients with periodontal
disease, we found a striking similarity between the striation
that you find in the joints with striation that is happening
in the gums of patients with periodontal disease.
Meaning that maybe there's a connection and
periodontal disease might be a source of the protein that
activates in your system.
As I mentioned before, the proline is a complexity
of all the bacteria that are in the mouth.
So the easiest question was to identify,
among all the bacteria, what are the worst that
are associated with periodontal disease.
If there's any one of these bacteria that may be able to
produce a citrullination process,
that we identify in the joints, and also we found in the mouth.
And in fact we identify one bacteria.
The name is aggregatibacter actinomycetemcomitans.
The name is complicated, took me a month just to remember it and
to pronounce the name, so don't worry about the name.
You can just call it A A, that is what we do.
So, here in this experiment is just to clarify these.
There's three different strains of these bacteria,
all bacteria that are known to be pathogens to.
And again, it's a very easy experiment you only need to be
a big scientist, you realize that it's a huge
of citullination that this bacteria.
So to understand the significance of these finding,
We develop an acid that allows to identify by testing
serum in the blood of patients,
which patient has been exposed to these bacteria.
And we identified that almost half the patients with
rheumatoid arthritis have been infected with AA.
Something that was even more exciting was that the majority
of these individuals, more than 90%, have evidence of
having a genetic predisposition for the disease, in addition of
producing antibodies against proteins that are citrullinated.
Which brings together this hypothesis of the interaction
between genetics, environmental factors, and the immune system.
So the hypothesis that we are working on is that at some time,
some individuals get infected with this bacteria.
Some of these patients are going to develop periodontal disease.
Not everybody that is exposed to AA are going to develop
periodontal disease.
Some are going to do it.
And if you don't have the genetic predisposition
to develop the disease,
you may stay just with the periodontal process.
And only in those individuals that have the genetics to have
rheumatoid arthritis, which are the minority.
Are going to move on to develop antibodies and
to develop the disease.
So identifying a pathogen is an incredible opportunity
in which we can intervene with therapies that can either
prevent the disease or modify the course of the disease.
So at this time what we are doing is trying
to define what is the significance of the bacteria
in rheumatoid arthritis.
And we might be able to target the bacteria to
modify the evolution of the resistance.
Before I do the acknowledgements, I would like
to mention that this is an incredible time for science.
It's just amazing.
We have the tools.
We have everything.
Trouble is, almost any disease
that has caused problems to humanity for centuries.
This is the perfect time to do it, and
we have the tools to do it.
However, we need to have the financial support to do it.
Not only to do our research, but
we need to train people that are going to continue with our work
when we might not be able to.
And we need young people that are aware that they will
invest 10 or 15 years or 20 years of their life.
And they will find the sources to continue working
otherwise nobody smart is going to do the search.
About acknowledgements, some information just to people
because they're the youngest one of the group.
And many people were involved in this work that had many
situations in America and outside of America.
One is Maximilian who is a young scientist,
a young physician in fact that came from Germany and
I have the privilege that he joined my lab.
And Loreto Abusleme, that she's a grad student at NIH that
is working with an incredible investigator, Niki Moutsopoulos.
So they are the youngest ones, and
they are the ones that are being trained to continue with work.
I also want to mention Tony who is the leader in our division.
And I won't go in detail because I don't want to
use too much of your time and take some time for questions.
So, thank you very much.
>> [APPLAUSE] >> Is there any question?
[INAUDIBLE] Yes.
>> [INAUDIBLE] >> Say it again.
>> Go to one of the mics please.
>> [LAUGH]
>> So in juvenile rheumatoid arthritis,
do you see the same prevalence of antibodies against AA?
>> Excellent question.
We don't know yet.
We are exploring different populations.
We need to expand this to other group of patients.
We don't know yet, but we will know soon.
And I hope that we will may find something, yes.
Excellent question.
>> And what exactly is rheumatoid factor?
>> Rheumatoid factor is an antibody.
That is targeting another antibody.
That is something that is quite interesting in fact.
It is that this is the first antibody that was discovered in
autoimmune diseases in the middle of the 1900s,
around 1945.
And I will say that we don't know which antibody it is.
We don't know how it's driving the disease.
It's an antibody that the proteins that is not specific
for rheumatoid arthritis.
It can be present in other diseases.
However, if you have it and you have rheumatoid arthritis,
your disease can be very bad.
And in our story, we find association with both in the,
with antibodies against proteins that are citrullinated and
also factors.
So it appears that rheumatoid factors and
AA may also be linked somehow to induce these antibodies, yeah.
>> Hi, thank you.
Is there a time connection between when someone's infected
with a periodontal disease and rheumatoid arthritis?
>> We don't know it yet, we will know it in three months maybe.
>> [LAUGH] >> So
we have access to samples from individuals in which the samples
of serum has been collected just before the.
So we will have an idea of the timing in which the individual
is exposed and the disease is clinically evident.
So we don't know yet but we will know.
>> I'll check back.
>> [LAUGH] >> Yes.
>> Yeah, I was curious, some of the news articles have connected
oral hygiene with rheumatoid arthritis.
Does any of that come from this?
>> Yeah we had a big media cover for this.
I think that newspapers everywhere here and
UK and other places.
This is the papers- >> Do you think supports
the idea that mouth hygiene is >> But
you know mouth hygiene is important for anything.
So independent of whether you may or
not have rheumatoid arthritis, mouth hygiene has been linked
to even cancer or cardiovascular disease.
So yes, it is critical.
I think that the hygiene is something that needs
to be done carefully, and you need to be checked by a dentist.
I think just doing it by yourself is not enough.
So someone needs to keep the teeth clean.
And yes, I think that a good hygiene is important.
But having a good one, and a good follow up by a dentist,
I think, is critical.
>> How could these findings with the interaction
between periodontal disease and bacterial
response potentially affect the sex specificity of RA symptoms?
>> So can you say it again, it wasn't fully clear to me.
>> So we know that rheumatoid arthritis affects more women
than men, how do the findings relate to that?
>> I don't think that the bacteria is going to make a big
difference on that.
I think that the gender differences,
the sex differences are, which is quite interesting.
Might be linked to other factors.
The immune system is quite different in woman and in men.
And woman may have a slow, in fact,
it's known that the immune system is more active in woman.
So maybe that, and there are some recent papers about it,
which are quite interesting.
So it is possible that women are just more predisposed to
autoimmunity.
Because it's not only rheumatoid arthritis.
It's also lupus and other diseases.
It's that women has an immune system that is more active and
therefore is more susceptible to develop an autoimmune process.
I don't think that the bacteria will be able
to address that point.
The difference of periodontal disease is not
major between men and women, in my knowledge.
So I think a correlation to women may be
explained by other factors.
Yes?
>> I was wondering if there's any evidence or any thoughts on
whether susceptibility to RA makes you more susceptible to
other autoimmune diseases, if there's any connection there?
>> What has been found is that in families, you can have
more than one patient with rheumatoid arthritis.
Or even there are patients that have other autoimmune diseases.
For example, the grandmother have Lupus and the daughter has
arthritis and somebody else has a thyroid disease.
So in autoimmune disease it is likely that
there are common genes,
common autoimmune genes that may predispose to have autoimmunity.
So the addition of external factors and
other things, gender and sex,
may also define which disease you are going to develop.
But this aggregation of different diseases in families
was something that we have seen.
And maybe it's driven by some genetic common defect, yeah.
Okay, thanks so much.
>> [APPLAUSE]