Bobbi Pritt, M.D. (00:04):

Hello, I'm Dr. Bobbi Pritt, a clinical microbiologist and laboratory leader at Mayo Clinic, and your host for today's episode. I'm excited to be here today with Mayo Clinic Laboratories’ CEO and president, Dr. Bill Morice, to discuss the latest news. And then, Dr. Julia Lehman will join us for a deep dive to share more about assays being used to improve care for patients with complex autoimmune skin conditions. So, let's start first with Dr. Morice. Bill, welcome back.

William Morice II, M.D., Ph.D. (00:33):

Great to be back as always, Bobbi.

Bobbi Pritt, M.D. (00:36):

And you know, this is an exciting week because it's Lab Week. We're celebrating the laboratories, and I wanted to just reflect on that. It's a great opportunity to pause and recognize the critical role that our laboratory medicine plays in healthcare. We know that a significant portion of medical decisions are based on laboratory results, and sometimes the clinical lab is called the engine room of the hospital. It's mostly unseen, but everything depends on it running smoothly. So, I wanted to get your thoughts on that. What parts of lab medicine do you think are perhaps least visible but essential to the broader medical community?

William Morice II, M.D., Ph.D. (01:13):

First of all, the word that comes to mind with Lab Week is one that I think is really essential just for good mental and emotional health. And that's gratitude, right? It's a wonderful opportunity for those of us who've been in the profession for a while to just express gratitude to our colleagues and the people that work with us in the labs every day. And that's all the way from getting a specimen drawn from a patient to operations, getting it into the laboratory, to testing, to the people doing the interpreting and developing tests, everything. So, I mean, there's so much that goes into it, and there's always a focus on the needs of a patient at the other end waiting for an answer or a doctor or a provider or someplace, somewhere, that we're going to really help guide their care. And also it brings to mind, I don't know if you recall, when I became the department chair at Mayo Clinic Rochester back in 2015, I gave my first talk, and that was the analogy I used, that we were the engine that was driving Mayo Clinic.

One of the great things about working at Mayo with our integrated practice is being in a laboratory, you are very aware of all the connections that we have throughout the hospital and throughout the healthcare system. They're kind of part and parcel to each other, that maybe others don't think about. Sometimes we don't even think about ourselves. That is so critical, and that is number one, that we do touch every part of the healthcare organizations that we serve. All the way from, you know, outpatient clinics to the hospital, from the neonatal intensive care unit, to ambulatory care to geriatric care. I mean, the whole gamut of what is healthcare, is supported by the laboratories. That's number one that I think is sometimes people lose that perspective because we think about our own narrow aperture by which we're interacting with the lab. And the other is just how much operationally is dedicated to getting high-quality, accurate test results and answers out to patients as quickly as possible. We can think a lot about tests and machinery and all these sorts of things, but it's all the people working in those systems to make them work for patients as effectively as possible. I think that to me is probably the thing that comes to mind.

Bobbi Pritt, M.D. (03:09):

Yeah, I love that. And I like what you said about just providing testing for patients throughout their entire lifespan. We are not just the doctor's doctor, but the patient's doctor. And we are providing care, laboratory results, for them often before patients are even born all the way throughout their lives. And there are not a lot of medical specialties that do that. So, I'll have another question for you. Really looking ahead is something we've talked about a lot, AI, data. As AI and data become more embedded in healthcare, how do you see the role of the laboratory evolving?

William Morice II, M.D., Ph.D. (03:49):

Actually, it will continue to amplify the role of the laboratory. And I just think of a couple of trends that AI is going to really enable for the laboratories to allow us to serve patients and society even better. One is a lot of work that you've done, I know in the infectious disease space, but thinking about detecting and diagnosing illness before someone comes to a healthcare setting, right? And I think we'll continue to see this push for diagnostics to be more widely available in more community-based settings, both for the early detection of disease. That's obviously a big focus in cancer. It's going to be a big focus on a lot of chronic medical conditions as well, in part fueled by GLP-1 and other drugs that seem to deflect or change the course of some of these chronic illnesses. And then the other, of course, is just in the laboratory itself, in the traditional setting, where you and I have cut our teeth, if you will, some of us having a bit long in the tooth, but anyways, but where I've cut my teeth, and that is taking all this information together and trying to give it meaning for a patient and for a provider. I think AI is going to really amplify our ability to do that, and to do so in a way that's really interactive. We spend a lot of time on the phone and it's great and I think hopefully we still will. I don't think any of these things replace human communication, but I think AI will really help us to have very focused communication with the providers, patients, physicians that we're serving to help them really understand the significance of the tests that they've already gotten and also what tests maybe they need to be getting as well.

Bobbi Pritt, M.D. (05:12):

Yeah, it's a critical role that we play in guiding testing and maybe even having test results before the patient presents or even before they develop symptoms ideally. Well, let's just end with a really inspiring story. I watched a video in which you were featured about a young patient named Isabel. And I love the story because at the end of the day, everything we do comes back to serving patients. Do you want to just say a word about her and her story in our last minute?

William Morice II, M.D., Ph.D. (05:40):

People should avail themselves of the video. It really is touching, even if you're not in the lab, especially when you're in the lab and thinking about the difference that we can make for patients. Isabel is a young woman who actually is in a family that's associated, I believe with health, maybe with Mayo Clinic and certainly with healthcare. She had a very odd array of symptoms that were really difficult to understand even when proximity to a place like Mayo. And it turns out that she has a very rare condition called congenital thrombotic thrombocytopenia purpura. And that's a mouthful. And it's one of these odd diseases. It's just low platelets. I think most people can relate to low platelets, low platelets in a child, but counterintuitively they also get blood clots. So, it's one of the rare conditions where you get blood clots and low platelets, and in this case it's caused by deficiency of a very specific enzyme that's required for maintaining homeostasis and clotting.

So, understanding that, making that diagnosis is really life –altering, because now they know how she can be addressed and treated. So it's just again, the ability to give an answer to a patient, right? Even if it's a one in a million patient, which this is the kind of thing that it is, it's just so impactful. And so that's why I think the video is just great, and you think of it for her, it's something you're diagnosing early, and it's going to be lifelong changing for her and lifesaving and really adding quality to her life.

Bobbi Pritt, M.D. (07:03):

Yeah. What a great story Bill, and a great way to close as we reflect upon this wonderful week of celebrating the laboratory. So, wishing everyone out there a very happy Lab Week.

William Morice II, M.D., Ph.D. (07:15):

Yeah, absolutely. Celebrate. You deserve to be celebrated, so celebrate.

Bobbi Pritt, M.D. (07:19):

Yeah. Thanks again, Bill. Talk to you next week.

William Morice II, M.D., Ph.D. (07:21):

Thank you, Bobbi. Sounds good.

Bobbi Pritt, M.D. (07:29):

Welcome to today's deep dive. We're thrilled to have Dr. Julia Lehman, a dermatologist and dermatopathologist at Mayo Clinic with us today. In this session, we'll look beyond the headlines and explore innovative tests developed at Mayo Clinic to diagnose autoimmune diseases affecting the skin. Julia, thank you so much for joining us.

Julia Lehman, M.D. (07:49):

Thank you for having me.

Bobbi Pritt, M.D. (07:50):

So, I'm going to just dive right in with our first question. The testing we're talking about today is for autoimmune blistering diseases. So, before we get into the details of tests, can you explain a little bit about what are autoimmune blistering diseases? I have to admit, they're always kind of on my differential when I'm also thinking about infectious causes. I'm very grateful there are people like you that focus in on these and really are experts in these areas.

Julia Lehman, M.D. (08:17):

Yeah, absolutely. So, it's a pretty heterogeneous group of diseases, but what they have in common is that all of them are caused when the immune system decides to attack the skin for one reason or another. And usually they're divided into two categories. One is if the autoimmune attack is at the basement membrane zone, which is basically the glue that holds the top layer of skin to the second layer of skin, or the epidermis to the dermis, that's called pemphigoid diseases. And then the other category of disease would be pemphigus diseases, where the autoimmune attack is against the glue that holds the keratinocytes or the skin cells together.

Bobbi Pritt, M.D. (08:53):

That's a good way to think about it. What are some of the common symptoms that patients experience?

Julia Lehman, M.D. (08:59):

That's actually one of the challenges with these diseases, is that they can present with a lot of different clinical manifestations. And so, for pemphigoid diseases, often they will present with tense blisters on a hive-like base, although they can just present with itching of the skin with no known cause. And also dermatitis-like changes of the skin. So sometimes the diagnosed can go months, even years, without diagnosis because if they have these unusual presentations, it can sometimes go undetected. Pemphigus can present with a number of different manifestations as well, including mouth sores or sores on the skin, or sometimes just rough scaly changes of the skin. So again, clinicians need to know that these diseases exist in order to be able to diagnose them properly in patients.

Bobbi Pritt, M.D. (09:47):

That's a good way to break them down, pemphigus and pemphigoid. So, you're an expert in diagnosing these. What led you to look for new diagnostic tools for these diseases?

Julia Lehman, M.D. (09:59):

Well, we're in a really exciting age for dermatology and medicine in general, in that now we have a lot more precise and safe treatment options for these diseases. So in the past, maybe it wouldn't have changed management, but now we can recognize various subcategories of these diseases, requiring the need for more diagnostic precision. And so that's why we decided to embark on trying to develop tests that can allow us to be more specific in which precise antibodies are involved, so that we can then help guide the clinician to select the appropriate treatment. The other major advantage to having diagnostic precision is that some of the subcategory of diseases will actually have other clinical associations as well. Some of them are associated with cancer or with other inflammatory systemic conditions. And so, knowing the precise diagnosis allows the clinician to know what else to look for as well in affected patients.

Bobbi Pritt, M.D. (10:53):

That's great. Can you tell me a little bit about how the team came together to design these new tools to address any diagnostic gaps?

Julia Lehman, M.D. (11:01):

Yeah, so you're absolutely right. It was a team effort to do this. So, the first thing was to recognize the need for the test. We decided to work with an industry partner on this. And so, it involved digging through our archives of stored specimens, because these diseases are very rare. And then screening them for ones that might potentially contain these antibodies, which is a little bit like looking for a needle in a haystack. But once we found some of those specimens, we were able to then test out the various assays that we were hoping to develop. And then after going through a pretty robust and rigorous process, we were able to demonstrate the sensitivity and specificity of the tests, reproducibility of the tests. And now we've experienced really pretty good results clinically as well, seeing that the test results correlate very closely with clinical outcomes. And so, it's been a really rewarding process, and I have to thank the team, including our development technologists, our quality specialists, our lab supervisor, and the whole rest of the lab team that came together to, to bring these tests to patients.

Bobbi Pritt, M.D. (12:06):

That's wonderful. I always love hearing stories about how you get a group of people together and that's where you know the real magic happens. So you have a test, tell us a little bit about it and how it's changed the way you care for patients.

Julia Lehman, M.D. (12:19):

Yeah, so the newest test that we have is an indirect immunofluorescence assay, or basically a serum test, where we incubate patient serum with transfected cells. And the transfected cells contain proteins that are the antigen targets for some of these rare autoimmune blistering diseases. In the past, we used to be able to just classify a patient as having pemphigoid maybe not otherwise specified, but now we can start to say, well actually, they've got one of these precise autoantibodies such as laminin-332 antibody, p200 antibody, collagen VII antibody. And although those proteins may not mean a lot to non-dermatologists or people who don't care for patients with these diseases, each one of those has its own implications for treatments and for associated symptoms for patients. And so it's very important to patients to know precisely what they have.

Bobbi Pritt, M.D. (13:12):

It's nice to be able to give them a precise answer. So, it sounds like this test has changed the way you care for patients. Can you talk a little bit about the benefits of this test?

Julia Lehman, M.D. (13:23):

Absolutely. So, we had a patient a couple of months ago actually, who had basically scarring changes of the eye, scarring changes in the mouth, and of the throat. With conventional testing, we were able to say that he had mucus membrane pemphigoid. By doing our additional assays, we were able to say specifically that he had laminin-332 pemphigoid. And what that means to the clinician is then that really warrants a deep dive into whether he has an underlying cancer. And so he underwent the proper testing and was actually found to have a tumor in his duodenum. By recognizing that, an asymptomatic tumor that may not have been identified for months potentially, by identifying that and resecting it, it made him much more responsive to treatment and obviously led to early diagnosis of another potentially serious problem. So, that's just one example of where the testing allows us to care better for patients.

Bobbi Pritt, M.D. (14:20):

Wow, that's a great story and just really emphasizes the importance of being able to make this diagnosis and then it leads to other treatments and diagnostics that may be done for these patients. So thank you for sharing this story with us. So I have to ask then, what are you thinking about for new diagnostics? What's next?

Julia Lehman, M.D. (14:39):

One of the holy grails of testing, laboratory testing for amenable diseases, is ocular pemphigoid. So, that's basically where you get an autoimmune attack against the conjunctiva, which can be devastating for patients. It can lead to scarring, lead to blindness. But one of the very big challenges to it is that none of our current tests are reliably positive for this. And so basically people caring for patients who have ocular pemphigoid have to make their best guess and then use potentially toxic treatments to halt the scarring process without having a confident diagnosis. So this is a huge problem. And so, we've decided to address this. And so we're partnering with some of our real expert colleagues in the Department of Laboratory Medicine and Pathology and at Mayo Clinic to try to develop sensitive and specific assay for ocular pemphigoid to find a new antigen target so we can be testing for antibodies that will help us get closer to be able to give a definitive diagnosis to these patients so that then the clinicians can be confident in proceeding with the appropriate therapies. So, this is pretty early in the works, just because it's such a novel test. But I think it'll really change the way that we can care for patients with a serious problem if and when we're successful in that.

Bobbi Pritt, M.D. (15:54):

Oh, I wish you the best with that. It sounds like a really important endeavor. Well, thank you again, Julia, for joining us and telling us what you've been working on, your successes, and maybe a little snapshot into what is on the list for next steps.

Julia Lehman, M.D. (16:07):

Wonderful. Thank you for having me, and I really enjoyed our conversation.

Bobbi Pritt, M.D. (16:15):

Let's wrap up with the top takeaways and how to learn even more on the topics we discussed. So, in recognition of Lab Week, Bill and I spent time discussing the essential role laboratories play in patient care and how that role will continue to expand as healthcare becomes increasingly data-driven. We also talked about Isabel's incredible story, which highlights the real-world impact of laboratory testing and what we do every day. And you'll find a link to that video in the show notes. And then in the deep dive summary, we were joined by Dr. Julia Lehman, who shared how tests developed at Mayo Clinic are helping her care better for patients with complex skin disorders. In the show notes, we've included a resource with more information on the immunodermatology test discussed in this episode. Thank you for joining us today. We hope that all of you have a meaningful Lab Week, and we invite you to join us for our next episode. Be sure to subscribe so you don't miss it.