Specialists check for compatibility of donors and recipients

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

Upstate University Hospital has a histocompatibility lab, also known as the tissue-typing lab.

Today I'm talking with its director, Dr. Reut Hod Dvorai, to learn about the role of this lab. Welcome to "The Informed Patient," Dr. Hod Dvorai.

Reut Hod Dvorai, PhD: Thank you so much for having me. I'm excited to be here.

Host Amber Smith: Well, I'd like to start by asking how you got started in this profession. I'm assuming you had an interest in science.

Reut Hod Dvorai, PhD: Yes, I think that's a very good question because the tissue typing is such a small niche, and I feel like most people don't even know that we exist.

We do all the work in the background, away from the spotlight, so getting into this field is kind of like ... you don't wake up in the morning and say, "This is what I want to do." You stumble upon it, I would say.

So the way I got into this field is, I went to school at the Technion, which is the Israeli Institute of Technology, and I did a bachelor's degree in biotechnology and food engineering. So, I envisioned a career in the food industry. And so the last year, I had an elective course in immunology, and I remember it very vividly. I was sitting in the lecture, it was the first lecture of the course, and the lectures started to talk about the history of immunology. And I just sat there, and it was so fascinating that I was, "OK, this is what I want to do."

So it was a total detour from what I thought I'm going to do. After that I did a PhD in immunology in the same institution, followed by a transplant immunology fellowship, and I ended up at Upstate.

Host Amber Smith: I appreciate you giving us that background and how you kind of found your way into clinical pathology. And this big word, "histocompatibility," that just means "tissue typing," right?

Reut Hod Dvorai, PhD: So, there are multiple different names. you can hear people call us the Histocompatibility Lab, the Tissue-typing Lab, we're also the HLA Lab. So either one of the terms is good to describe us.

Host Amber Smith: Let's talk about what tissue typing is and what it's used for in medicine. Can you tell us about the history of tissue typing and how it began?

Reut Hod Dvorai, PhD: Sure. I'll start by explaining what tissue typing is. Tissue typing is essentially a process where we take blood from a person, and we test the blood for their human leukocyte antigens, so, HLA for short. And HLA are proteins that are expressed on the cell surface of almost all the cells in the body. And they help our immune system to distinguish between self and non-self.

So you can think of HLA proteins as a passport that every cell in our body carries, and it shows this passport to our immune system, letting the immune system, which is our body's police, know that it's healthy or not. If the cell is not healthy, or (is) infected with a virus, for example, it shows it to the immune system and then the immune system can target and eliminate this infected cell.

So it basically helps us to protect our body against things that are not supposed to be there, but at the same time, it helps our body protect healthy cells and tissues.

Host Amber Smith: So is this a science that emerged alongside organ transplantation?

Reut Hod Dvorai, PhD: Yes, absolutely. Organ transplantation, in the modern era, it began with observations of skin graft rejections in patients. Those were soldiers and civilians during World War II. So, at that era, there were a lot of people that were burn victims, and clinicians noticed that when you put a graft on a person, if it comes from the same person, the graft is usually accepted or tolerated. But if you take a graft from a different individual, then the graft is usually rejected.

And so, slowly they began to understand the basic concept of transplant immunology. And the progress of surgical techniques and medicine in general, and development of new drugs, all of that made transplantation possible. Histocompatibility came a little later. The first observations that led to the discovery of the HLA, or tissue-typing, system in humans came from patients who were either pregnant or had multiple transfusions. And so these individuals, they noticed that when they get blood transfusions that had white blood cells in them, they would often react against the white blood cells. But when the white blood cells were removed from the transfused products, the transfusion reaction didn't happen.

So they realized there is something on the white blood cells (leukocytes) that makes people react against. And, the first description of the human leukocyte antigens, or HLA antigens, came in 1958. the first successful kidney transplant was in 1954, four years earlier, so they didn't even know about HLA when they transplanted the first successful kidney, but their luck was that the recipient and the donor in that scenario were identical twins, so they had the same HLA, and that was one of the reasons why the transplant was successful.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Reut Hod Dvorai. She's an assistant professor and the director of clinical pathology -- histocompatibility at Upstate.

Why do you have to determine HLA compatibility prior to transplant?

Reut Hod Dvorai, PhD: Because our body knows to recognize our own kidneys as self. The problem starts when we put a kidney from another individual into our body, and that kidney expresses different tissue types, our different HLA antigens.

And at that point our immune system looks at the kidney and recognizes something that is foreign that shouldn't be there, so it starts attacking and wants to reject that kidney. So, in order to avoid that, we want to match between donors and recipients. And there's a few testings that we perform in the lab to do that.

The first test is we do HLA tissue typing for the donor and the recipient to determine how well matched they are.

The second test that we perform is HLA antibodies present in the serum (the liquid part of the blood) of the recipient. And basically we want to know if the antibodies that the patient has are aimed against a specific donor.

And the third type of assay that we perform is what we call a crossmatch. That's an assay where we actually take blood from the patient and blood from the donor, and we incubate them together to look for reaction.

Host Amber Smith: So, is this histopathology done when a person joins the transplant waiting list, or do you wait until you think you might have a match with a donor?

Reut Hod Dvorai, PhD: So, that depends on the testing. So, the tissue typing is done at the very first stage, when the patient presents at the transplant clinic for evaluation. They take the blood, and they send to the HLA lab. We do the tissue typing one time, because tissue typing, it's a genetic test, essentially. We test the DNA for the HLA genes, and so the DNA doesn't change; we only have to do that one time, at the initial stage of evaluation. And then we test for the presence of HLA antibodies in the patient's serum. But in order to be up to date, because antibody profile of the patient may change over time, that we have to repeat every three to four months. So while the patient is waiting to be transplanted, he's waiting on the wait list, we need to update his antibody testing every few months.

The crossmatch assay is only performed when there's an actual donor, or an actual kidney offer, for that recipient, because then we take the specific donor and the recipient, and we look for reaction between them.

Host Amber Smith: We're talking about kidney transplants, but would this be the same whether it was a liver transplant or a heart transplant? Do you have the same sort of concerns and tests?

Reut Hod Dvorai, PhD: So, we perform the same testing for the different types of organs. The concern for rejection itself is slightly different between the different organs.

So, for example, liver is an exception. Liver has a lower rate, or a lower risk, for rejection because it has this amazing ability to absorb antibodies, and it's more resistant to rejection. But even the liver can be rejected.

For hearts, for example, transplant centers may choose to take more risk when it comes to transplant because when the kidney fails, there's an option to continue care on dialysis, long term. When the heart fails, there's not many options, so it's more medically urgent, and so you might be inclined to take more risk.

Host Amber Smith: Now, are you working with blood samples, or do you need actual tissue to examine, to do the histocompatibility?

Reut Hod Dvorai, PhD: So, we usually test a patient's blood. We isolate the DNA from the patient's blood, but we can also use other types of samples, such as cheek swabs, or we can use saliva, too.

Host Amber Smith: We've always heard, like with transplants, that the donor and recipient, their blood has to match. Is that the case? That the blood has to match, and then, on top of that, you have to have a tissue match as well?

Reut Hod Dvorai, PhD: Yes. The blood group system, the ABO blood group system, is totally separate of the HLA antigens. So those are two separate things.

So for transplant, we try to match for both. We try to match for the blood group, and we try to match for HLA.

We can sometimes do transplants across what we call ABO incompatible pairs. So, that means that there's not necessarily a match of the ABO blood group system. But with HLA we try to avoid situations where there's incompatibility, meaning that the recipient has antibodies against the HLA antigens on the donor cells.

Host Amber Smith: Are twins always a match?

Reut Hod Dvorai, PhD: Identical twins are. Identical twins will have the same HLA because they have the same genes. With non-identical twins, it's a 25% chance of having the same HLA, same as just regular siblings. And in general, within the family you have 25% chance of having an HLA-identical sibling. You have 50% chance of having a half-matched sibling, and you have 25% chance of having a sibling that has nothing shared with you.

Host Amber Smith: So that's for siblings. Would that be the same for parents or aunts or uncles or grandparents?

Reut Hod Dvorai, PhD: The HLA genes are inherited from the parents.

So that means that you get one gene from your mom and one gene from your dad. So, essentially, the parents are always half matched. So 50% match always.

Host Amber Smith: Does the person's gender affect the match?

Reut Hod Dvorai, PhD: It shouldn't. No, those are two separate things. So you can be male and female, and you can have the exact same HLA typing, or you can be two females but have a different HLA typing.

Host Amber Smith: So, what is the likelihood, if you are on the waiting list for a kidney transplant, what is the likelihood of finding an HLA-matched donor?

Reut Hod Dvorai, PhD: I'll start with first saying that we don't look for an identical donor when it comes to organ transplants. That's a different case with stem-cell transplants, but for solid organ transplants, we can't find, it's just not feasible to find, someone who has the exact HLA as the patient because the HLA genes are so diverse. There are thousands of different variants of those genes, which means that different individuals have different HLA types, so having someone that has the exact same HLA, it's very unlikely to find, especially if it's an unrelated donor. So, we're not looking for an exact match.

The one thing that we want to focus on when we determine compatibility is looking for antibodies in the recipient and making sure that these antibodies are not aimed against the donor HLA. So a patient can have HLA antibodies, but as long as they're not aimed against the specific donor that we're evaluating for that patient, that should be OK.

Host Amber Smith: So does a strong tissue match with a transplanted organ, does that reduce the amount of anti-rejection medicine an organ recipient has to take afterward?

Or does it improve the chances for a successful transplant?

Reut Hod Dvorai, PhD: Yes, absolutely, 100%. As a rule of thumb, a person cannot develop HLA antibodies against their own HLA, so if your donor has the exact HLA as you, then you won't be able to develop antibodies against your donor, which means that you are very unlikely to reject the organ, which means that you can probably be managed on lower immunosuppression, which is a good thing for patients because immunosuppression has its tolls. It makes you more susceptible to infections and malignancies, so having lower immunosuppression is something very beneficial. So, the better the match is going to be, the better the outcome is going to be.

Host Amber Smith: Well, thank you for taking time to explain this to us. I appreciate it, Dr. Hod Dvorai.

Reut Hod Dvorai, PhD: Of course. Thank you for having me.

Host Amber Smith: My guest has been Dr. Reut Hod Dvorai. She's an assistant professor and the director of clinical pathology -- histocompatibility at Upstate.

"The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe.

Find our archive of previous episodes at upstate.edu/informed.

This is your host, Amber Smith, thanking you for listening.