Rethinking Immunodeficiency

Listen to the episode Rethinking Immunodeficiency hosted by patient advocate Abbie Cornett. In this episode, we'll be exploring how what we traditionally call immunodeficiency is actually part of a larger spectrum of immune dysregulation. Our guest today, Dr. Kobayashi, is a clinical professor at the University of California, Los Angeles, School of Medicine, and is an expert in diagnosing and managing complex immune disorders.

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Welcome to today's podcast! My name is Abbie Cornett, and I am the patient advocate for IG Living magazine. This podcast is brought to you by IG Living to give readers the chance to hear directly from healthcare experts on topics that matter to them most.

Abbie: In today's episode, Rethinking Immunodeficiency, we’ll explore how what we traditionally call immunodeficiency is actually part of a larger spectrum of immune dysregulation.

Our guest, Dr. Kobayashi, is a clinical professor at the University of California, Los Angeles, School of Medicine. In addition, he is a national consultant for the Immune Deficiency Foundation and is on the executive committee for the Consortium of Independent Immunology Clinics. Dr. Kobayashi is an expert in diagnosing and managing complex immune disorders. Today, he’ll help us unpack how immunodeficiency, autoimmunity, autoinflammation and allergy may not be separate conditions — but rather interconnected responses within a dysregulated immune system.

Abbie: Good afternoon, Dr. Kobayashi, thank you so much for joining us today. I’m really excited to dive into this important topic. So many people talk about immune deficiency and autoimmunity. Can you explain what we mean when we talk about immune dysregulation and how it challenges the traditional way we think about what primary immunodeficiency is?

Dr. Kobayashi: Yeah, I think that's a great question. And the thing is that, classically, we have separated these four entities. And really, I think we've done it rather naively, because when you look at the immune system, its main function is to recognize self from non-self, and harmful organisms and substances from non-harmful substances. For example, the food we eat, the creams we put on, our immune system tolerates that. And I look at it as its primary defense system. And when something goes wrong in any of the self-recognition or tolerance to oneself and tolerance to harmless things in the environment or food or creams versus harmful bacteria or harmful cells within us, like harmful bacteria, parasites or cancer cells or abnormal cells for other reasons, then the immune system, you can clearly think of it as being if something is not regulated correctly, any one of those manifestations can occur. So what happens? So if you cannot recognize something that's harmful, that would be immune deficiency because you can't recognize something that's harmful. What do we mean by autoimmunity? Here, we are attacking ourselves, and there are mechanisms for that which we'll go on in detail later. Now we talked about harmless things in the environment like food, creams, things that we get exposed to that we normally would not react to. And we have cells that cause us to tolerate these. But you can imagine if our immune system is defective and does not tolerate these anymore, then we have things like allergy, where why in the world would you react to a pollen or mouse dander or peanuts or eggs? And the final component, I look at it like four legs on a table. 

The final and important aspect is inflammation. And so, sometimes, if something's wrong with your immune system, you can have exuberant inflammation where it's too much. It's kind of like you have a fire in your kitchen, and instead of just getting the fire extinguisher and aiming it right at the fire, the fire department comes, they break down their door, they flood your whole house and they wet everything. And this is kind of like exuberant inflammation. The other thing is that sometimes our inflammation, it's supposed to turn off and sometimes it doesn't. And so what happens is you have chronic inflammation. And a lot of our diseases, autoimmune diseases, are characterized by this. And sometimes infection will come in; we have an inflammation, it gets rid of the infection, and then it's supposed to shut off. But then you can imagine if your immune system is defective or not regulated properly, you could be attacking the wrong thing — like instead of attacking the bacteria also, you start attacking the lungs or the kidneys or your joints. And it's thought a lot of times in the activation of inflammation and autoimmune diseases, an infection may trigger it. For example, in rheumatoid arthritis or rheumatic fever where strep may be involved. And so you can see it's rather a spectrum. So to think of it as separate entities, I think was not correct. And if you look now, all of the immunologists, particularly the Europeans, but also people here in the United States — Kate Sullivan from CHOP, Troy Torgerson who moved from Seattle — these are individuals the Eastern European Society of Immunodeficiency have been talking about this for years. 

Abbie: Well, I know that before that conversation really became public, patients with immune deficiency frequently are like, well, how can I have an allergy or how can I have arthritis or lupus? I have immunodeficiency. And that question has always been in their minds because it seems like there's a disconnect. On that, let's talk about this broader spectrum. How are immunodeficiency, autoimmunity, autoinflammation and allergy connected? And why is it important to look at these not as a separate category when it comes to treatment, but as points along a continuum of immune  imbalance within the body. 

Dr. Kobayashi: Yeah, I think that's another great question. To answer the first part of the question, I think in the old days, it was simpler and perhaps effective to look at these as separate entities. And part of the result was specialties arose from focusing on these special issues. So for example, when you had allergy, we had the specialty of allergy and asthma. With immunology or immunodeficiency, you had the specialty of clinical immunology. With autoimmune diseases, you had the specialty of rheumatologists and, more increasingly, gastroenterologists and others. And then inflammation fell into that sort of broad category. 

The problem is that everybody kind of focuses on their own area, number one. And so as an allergist, you never thought of immune deficiency because you're thinking about the abnormal response to so-called harmless things in the environment. And even now, I mean, if you look at, I think the Immune Deficiency Foundation did a survey many years ago, where maybe 5 percent of the allergists that were going to the Academy meetings were treating a lot of immune deficiency patients. And many times, the allergist would not even recognize somebody who had immunodeficiency.

Abbie: I was going to say, I can speak from personal experience. I was going to an asthma specialist and getting worse and worse until I came to you and you were able to say, wait a minute, this isn't asthma. 

Dr. Kobayashi: Yeah, I think that, you know, again, everything is interconnected. For example, if you have a lot of infections, that may trigger your immune system. And if you have problems in regulating the inflammation, then you develop chronic inflammatory lung disease, for example, chronic inflammatory liver disease. In the case of arthritis and other problems, chronic inflammatory joint diseases and connective tissue disease, and the gut. I mean, if you look at the gut, it's been said that we have about two pounds of bacteria in our gut. So our gut is constant. I'm amazed more things don't go wrong in the intestine — I mean, given that we have all these bacteria and the vast, vast majority of them are very important. We've talked about intestinal microbiomes, development of the immune system and a number of other factors. But the immune system is very potent and active, and there's tons, so if you look at the gut, it's just loaded with immune cells. And they have to recognize the good bacteria from the bad bacteria, the good food from the bad food, and all of these kinds of things. And if they're constantly getting infected, inflamed, damaged for whatever reason, you can foresee inflammation turning on — inflammatory disease with Crohn's disease, inflammatory bowel disease of all kinds. The same thing can happen in the lungs. I mean, if you look at patients with chronic inflammatory lung disease, the next thing you know, they get an infection, the immune system turns on, and if it keeps turning on and turning on and turning on, somewhere, someplace, it's like a switch. The switch may not turn off. And all of a sudden you have a chronic problem. 

And the thing is that if you look at the gut, you look at the respiratory tract, that's where a lot of the bacteria and the foreign organisms come in. And the skin. And that's where your body puts the defense. But it’s complex, you know. Imagine you're working at Chicago O'Hare and there are millions of passengers coming all the time, and you have to pick out the potential person that is going to do you harm. 

Abbie: And some slip through.

Dr. Kobayashi: Well, what happens with our immune system. We do the same thing. We have these regulatory cells, T cells that recognize cells that are supposed to be there, cells that are not supposed to be there. And we tolerate certain things. It's kind of like we tolerate passengers who are not going to do us any harm. And then we're supposed to recognize the so-called terrorists. But what happens if you got some crazy guy and he starts saying, well, everybody's a terrorist. So he starts shooting everybody that comes, innocent or non-innocent. Well, you can see the immune system kind of doing the same thing. Or you can have the immune system so turned on that it becomes hyperactive. And I had that experience in Los Angeles. I reported a stolen license plate in West Hollywood because they delivered my car at the wrong place. Unbeknownst to me, they had a shooting right outside the police station. I didn't know that. I walked into the police station to report my stolen license plate. The officer drew his gun. I said, well, I'm just here to report a stolen license plate. He kind of looked at me like I was the craziest guy on the face of the earth. He says, look, we've got a shooting out here. I'm not going to be worried about your license plate. Well, you can see that if the immune system is hyperactive, it'll be like the policemen. Or if you have people, you know, soldiers in the jungle, and they don't know who's the good guy versus the bad guy, they shoot everybody. Well, the immune system can go wrong that way also. And so you can have chronic inflammation. And this is a huge problem. And, we'll talk about this a little bit later. But in many of the immune deficiency diseases, autoimmunity, chronic inflammation and asthma all go together — with Scott Aldridge being the classic example of patients with eczema, autoimmune disease, and immunodeficiency. They can't fight, you know, encapsulate bacteria. It's been said that, you know, and the Europeans, really, I think they're ahead of us on this. They have these gigantic databases, and there was a recent publication where they looked at 16,000 patients in their database. About 60 to 70  percent of the patients presented initially with infection. But the other 30 percent presented with something else. They presented either with autoimmunity or a combination or with syndromic features such as the DeGeorge syndrome where they have features in their face, or there are other immune deficiency diseases where they may have abnormalities in the heart or elsewhere first before they develop immune deficiency. And these things are missed. And the argument is why should you be thinking about these unusual presentations. In other words, they can co-exist. You can have all four or you can have something presenting initially and you're treating one thing without recognizing the other. 

Abbie: That's really interesting. It’s amazing. Some of the technology that they're using now to connect the types of diseases that you just talked about from the initial presentation, but that'd be a whole other podcast. As you already talked about, immune deficiency patients, especially those with primary immune deficiencies, frequently see overlapping symptoms where they might have both low antibody levels and autoimmune symptoms. How common is this overlap? And you mentioned that there is quite a bit of overlap. But how much overlap is there between immune deficiency, autoimmunity, inflammation and allergies? And how does that overlap impact diagnosis and treatment? Do the treatments remain the same for people who have immune deficiency, but then also have RA as an example? 

Dr. Kobayashi: Yeah, you know, again, that's a great question. I mean, it's amazing, but the overlap is quite remarkable. You have diseases like IPEX and AIRES, these extraordinarily rare diseases, and there's good discussion describing that on the internet. And a gene or a disease called AIRES syndrome, where they have immunodeficiency and a 100 percent autoimmunity. But let's take a common disease like CVID, which is what most people have. it's the most common of the severe immunodeficiencies, one in about 25,000 or so. Anywhere from 25 to 40 percent of these individuals have autoimmune disease. And sometimes may present initially with autoimmune disorders.

Abbie: I didn't realize it was that high. 

Dr. Kobayashi: Yeah, I mean, it's high. Kathy Sullivan gave a great lecture. She gave 40 percent. If you look at the European data, you know, it's about 25%. It depends on who you look at. But it is high. 

If you look at the classic antibody disease, which is XLA, Bruton’s agammaglobulinemia, where their B cells are defective, so they don't manufacture, either they don't manufacture antibodies or they don't manufacture enough antibodies. Anywhere from 10 to 20 percent of these individuals also have autoimmune disease, most commonly in the gut or in the blood. And so, you know, these are not rare and they have, again, diseases like CTLA where they have autoinflammatory disease and then they develop immunodeficiency. So a lot of times they get misdiagnosed, they get mistreated. 

So to answer the second part of your very important question, and this is something that bothered me 40 years ago, and when I was trained, it was counterintuitive. You had these patients with CVID who had granulomatous disease in their lungs and whatnot. And Dr. Stiehm, who trained me, would give steroids, and I'd say, wait a minute, wait a minute, you're gonna make it worse. And that's the conception we had, and it was completely wrong. It was their T cells — their immune cells were overactive. And so you had to give medications such as steroids or immunosuppressants such as Imuran and Cytoxan. I mean, it's counterintuitive. They have immunodeficiency. They don't have enough immunity to fight infections. Why in the world are you giving them steroids which suppresses the immunity or Cytoxan or Imuran or all of these kinds of immunosuppressants? 

Well, it's because the immune system is overactive. And in some of these diseases, they have T-regulatory, you know, the T cell is a lymphocyte, and when you look at it under the microscope, it doesn't look like much. It just looks like a blob. But this is the quarterback for the immune system. I mean, you know, if anybody was underappreciated and doesn't look like much, you know, it's kind of like this, I don't want to sound sexist, but this homely grandmother teacher that doesn't look like much from the outside, but has a ton of stuff on the inside. The regulatory T cells are just like that. They're the commander. They tell everything what to do. And if they're defective and they're putting out all kinds of signals of inflammation or they themselves, cytotoxic T cells are attacking organisms, you got to shut them down. And you shut them down. You shut them down with steroids and Cytoxan, and all those kinds of things, which is counterintuitive. But in the past, we used to treat incorrectly. And I think one of the key points from this discussion is that the recognition that immunodeficiency, while infections are still the most common, and even infections, you've got to get tons of them before somebody finally diagnoses you. Heaven help you if you have something different like autoimmune disease first, or immune disease and you happen to have a little more infections. Or you have infections and you have inflammatory bowel disease and everybody says, you hmm, you know, we'll send you to all these different specialists. Wrong. 

Abbie: You should be looking at it as a continuum of one disease. 

Dr. Kobayashi: Yeah, and you know, I want to make a pitch for immunologists. I always used to tell my specialist friends, you know, I don't do anything, but I'm kind of like your wingman. You know, I'm flying protection for you because you're so busy taking care of cancer and, you know, inflammatory bowel disease and severe lung disease. But I'm kind of the guy that's saying, hey, wait a minute, wait a minute, you know, maybe you ought to be thinking about this. Maybe you ought to be thinking about that. 

I think, put in a pitch for immunologists, I think, they have been the ones at the forefront. And, they're doing it more and more now. I mean, the Academy is putting on these meetings, CIS is putting on these meetings, the Europeans are putting on these meetings where they're getting the rheumatologists, the cancer specialists, the gastroenterologists, the ENTs and the immunologists and the allergists all together in these joint meetings. And when I was teaching full time, I used to think, well, you know, how boring talking to, I shouldn't say this, but allergists. You know, we only talk about asthma and sneezing. I mean, I want other guys to be around, know, other people to be around. You know, I want to hear what the ENTs are saying because, you know, they have chronic infection. Maybe that person has immunodeficiency disease, or they may have chronic inflammation as a result of their immune system not turning off. Or their immune system might not be quite perfect, so the bacteria is not quite cleared. So the immune system is constantly being stimulated. All of these kinds of things, you've got to be thinking. 

Abbie: I remember you used to use the analogy that when there's chronic infection, that immunoglobulins are a little bit like a bathtub that doesn't have the plug in it. And it just continually keeps going down and down until there's nothing left. I don't know if you remember using that analogy. 

Dr. Kobayashi: Yeah, there was a famous you know, song, you know, them bones, the shin bone is connected to the knee bone. And I think with all these super specialists, you know, we went to the Mayo Clinic and I liked the Mayo Clinic. I think they're terrific. But, you know, they've got about 200 pulmonologists and everyone is, you know, one is interested in one part of the lung, another one is interested in another component of the lung and … 

Abbie: They're not looking at it as a holistic approach.

Dr. Kobayashi: They're not looking at the whole body. And I think it's the same thing. We need people to look at the whole system and say, how is this all connected? Not only in terms of symptoms being presented, but proactively and prospectively. In other words to look, OK, you have CVID. There are patients who will develop autoimmunity and cancer, and therefore, you should be proactively and prospectively doing studies. And out of the 300 plus patients I was following with antibody problems, I think we found two dozen who eventually developed lymphomas and other lymphoproliferative diseases. We found a number who developed arthritic or rheumatoid issues. 

And so these things need to be looked at. And we did blood tests. And, you know, people would say, well, like, why are you getting protein electrophoresis? Why are you getting this? Separate or something. I said, because we're looking for chronic inflammation or inflammation that was being hidden. Because what are the symptoms? I mean, when you have lymphoma, how do you know you have lymphoma until you get tired or you hurt somewhere? And by the time you're tired and you hurt somewhere, the darn thing has spread all over. Isn't it better that if I know you have CVID that I look for the possibility, even if I keep ordering tests every year, looking for this rapid cell turnover or inflammation, and if it's abnormal, say, you know, we don't want you to get worried, but you should check. 

The same thing on the flip side. You know, we've had patients who were referred from rheumatologists, but we found out they had immunodeficiency. And so you have to treat that. And a lot of these diseases now, because of the advent of genetic analysis, we're beginning to treat them completely differently.

Abbie: That kind of brings us to the next question. We've talked about the importance of rethinking how we look at immune deficiency and autoimmunity. The question is how do we screen and manage these patients, and what role do genetics, environment and, you've touched on this a little bit with gut health and microbiome, play in shaping immune dysregulation across the spectrum of the different diseases?

Dr. Kobayashi: I think it's critical. And the thing is that, with genetics, the basic scientists and the academic immunologists and oncologists and others are beginning to do genetic screening panels to see. And there are a number of these panels now available. And before I stopped seeing patients, we were ordering them for every patient we saw because we were thinking, could they be, you know, something that we want to watch for? And the reason being... If you have, let's take something simple. If you have antibody deficiency, CVID or XLA, you would say, well, yeah, you know, we'll give you immunoglobulins. We have a great treatment for that, and you don't have to worry. Well, wrong. You know, there are patients that, you know, you give gamma globulin to and they still have complications — they have chronic lung disease, they have inflammatory bowel disease, they have cancers and all of these kinds of things. And so I think it is incumbent that we use the best we can how to determine what categories these different patients fall into. I mean, if you look at CVID, for example, which is the most common of the severe immunodeficiencies, it's kind of like a garbage can diagnosis. I mean, you throw everything in there. You don't make antibodies. Yeah. You know, and you're older. Yeah. You've got CVID. 

Abbie: Nobody has the same CVID. That's what I try to tell people. Everybody's different. 

Dr. Kobayashi: Yeah, there's some where you give gamma globulin. They're sick all the time, you give gamma globulin, and all of a sudden they're perfectly healthy. There's some you give gamma globulin and they're still sick and develop all kinds of other problems. And so we're discovering more and more, even in CVID now, there are about 20 percent where they have some genetic markers for that. And eventually we'll find more and more. You know, there are over 500 genetically defined immunodeficiencies. And people would say, well, so what? It's so rare. I'm too busy. I'm worried about obesity or, you know, all these other kinds of things. But if you look at immunodeficiency, if you look at autoimmune disease, these are not that rare and they're extremely expensive. And the longer you delay diagnosis, the more expensive it becomes. 

Then, doesn't it make common sense that if you have these patients that fall into this broad spectrum, that you kind of look to see what they exactly have. So one, you can treat them correctly. Number two, you know what might happen to them. And so you watch out for it; you try your best to prevent that. I mean, even simple things like infection. We know that chronic infection drives the immune system, the more you drive something, the more things go wrong. It's kind of like your car, you know. The more you drive it and the harder you drive it, the more stuff is going to go wrong. It's the same thing with your immune system. The more it gets turned on, the more it gets stimulated, the more it gets bothered, stuff can go wrong. And so what happens if you have somebody that you don't treat the inflammation, you don't treat the infections, you don't proactively look out for these things, you get into bigger problems. And I think that's the key. Genetics is the key. Targeted treatment is the key. 

Abbie: This brings us to the last couple of questions. This broader view of immune dysregulation has big implications for treatment. How do you recognize the spectrum approach and create more effective treatment plans for individuals, especially for those patients who you were just talking about that don't neatly fit into one diagnostic box? 

Dr. Kobayashi: Yeah, I mean, that's a hard question. But, I think the first thing is you need to get rid of the old idea that everything is in these nice neat compartments. You have to think, and this gets back to the fundamental topic of immune dysregulation. You have the immune entity that is not functioning perfectly like it should. And something so simple, in fact, most immune deficiency diseases are a very narrow spectrum. But just one cell, for example, the T regulatory cell, which is abnormal, can cause all kinds of downstream problems. It's kind of the same thing. 

Since we're worried about the FAA and air traffic control in Newark airport, let's use that as an example. You have hardworking people. My father was chief of communications at the Pacific Basin. So I kind of have a soft spot for the FAA. But if you have these people who are overworked or haven't helped you, if you have somebody who has mental problems or someone who kind of goes berserk. I mean, can you imagine, and that person is in control of Newark airport and the airspace around it? I mean, planes will be crashing, things will be happening, all kinds of problems. Well, it's the same thing with the immune system. One cell, and sometimes often just one gene or one protein or one signal, one signal that's defective can cause downstream catastrophic effects of many kinds of problems. 

So what should be done? I think it is incumbent upon us to do research into finding out more and more. What are the fundamental problems so we can get at the fundamental issue. The example I used 40 years ago is when you put your key in the car and it doesn't start, you don't automatically put gas in all the time. I mean, shouldn't you check up on everything else that could go wrong with your car? It's the same thing. 

The other thing that I think is important is you cannot just depend on the doctors and the healthcare system, because now the doctors are so fragmented, they're so busy, they're so focused on their area for whatever reason. And the healthcare system is fragmented and communications are more difficult, I think. The patients have to take it upon themselves also. Number one, why am I getting so many infections? Why am I getting infections and allergies? Why am I getting infections and stomach problems? Why can't I get rid of these sinus infections, and why am I always having trouble feeling tired and all of these kinds of things? I mean, everything can be interrelated. 

And I think COVID was a perfect model. You had millions of people getting infected with the same microorganism. And the manifestations were multiple. I mean, it was just amazing. I hate to say it, but it was just a wonderful experiment in nature where you saw one organism attacking millions of people at the same time. And you found out that a lot of people never got sick. Some people got kind of a little cold. Some people got bronchitis and a little pneumonia. And yet some people had all kinds of problems. I mean, look at the long COVID, look at the autoimmune problems that we had with COVID. To me, one of the fascinating things is that very few people knew about interferon gamma deficiency because it was so rare, and then all of a sudden, we get COVID and then you get all these people who would find out they had gamma interferon deficiency. And they got an overwhelming viral infection. And then, even more incredible, is that the COVID virus caused autoimmunity, and the immune system made a mistake, attacked gamma interferons. So your own immune system got rid of the very protein that's supposed to protect you, and then you got overwhelming. And so you can see all of this interconnection that we need to look at and treat properly. 

Abbie: We're going wrap it up here, but there are a couple other things I want to touch on real quickly. How can patients advocate for themselves? That's always pretty much how I finish my topics. How can patients advocate for themselves and work with their medical team to gain a more complete understanding of their condition? 

Dr. Kobayashi: You know, again, that's tough. But I think the patient has to do it. The patient has to be informed. And there are a number of organizations that help with informing. The IDF [Immune Deficiency Foundation] being one of the major ones, certainly the Jeffrey Modell Foundation, the ESID, the Europeans. 

But I mean, it's incumbent upon the patient. You cannot take a passive view as, my doctor will take care of it. Your doctor is busy. They've got thousands of patients to deal with. And now the superimposition of medical record keeping and all this other stuff. And so you have to inform yourself. You have to educate yourself. And there's tons of stuff on the Internet.

And you have to go to reliable sources because wrong information is more damaging. In fact, I think they did a study to see why a lot of mothers did not want to have their kids vaccinated. And these mothers weren't stupid. They weren't cruel. They weren't, you know, they wanted the best for their kid. But they read the wrong information. So getting the right information is critical. 

Abbie: That's the first thing I tell a new patient who says, I just was diagnosed, what do I need to do? And I said, learn everything you can about your condition because you are your own best advocate. I can help you, but you need to advocate. 

Dr. Kobayashi: Yeah, and bring it up to your doctors. I mean, do it in a polite fashion, but ask because who is most interested in you? It’s you. You can't sit like a, you know, a toad on the stone hoping that you won't get run over by a car. I mean, you’ve got to get going. 

The other thing is that you have to somehow publicize this. And, and, I don't know whether Joseph Stalin said this, you know, he said: A million deaths is nothing. One death is a tragedy. 

And I think a lot of times like Ryan White with AIDS and Rock Hudson and all of those people, you know, we've had, what, 40 million people dying from AIDS, what does that mean? But if you focus on the individual. If you tell a story in an effective way, if you get involved in organizations and particularly with the legislative organizations to put pressure on the healthcare system, put pressure on the insurance systems. Because I mean, the insurance is critically important and they serve a number of useful roles. But, you know, their default position is no. And so, they're not the bad guys. It's just, you know, things have evolved. 

But you have to put pressure on them to say that this is important to prevent. I remember about 15 years ago, we went to IDF and said, we need a national meeting with the people, with the insurance companies who have the power to make general policies, because otherwise we're wasting our time arguing on an individual basis. And it took about 10 years before we finally got it done. And the insurance company told us: That's not really our problem for a number of reasons. Well, it is a national problem because if you don't take care of this thing correctly, like you said, downstream, it'll cost us a ton of money. I mean, if we can prevent serious complications from something so simple as CVID and using gamma globulin, for example, and preventing chronic lung disease, looking out for inflammatory disease, bowel disease, looking out for lymphomas, etc. Catch these early. We're preventing a lot of downstream expense. 

OK, well, I think it's important that people get rid of the old way of thinking. Immunodeficiency is really a broad spectrum. It's immune dysregulation, the inability of the immune system to function properly and in itself cause disease. I think it's important also to be your own advocate. It's also important for you to be informed about your disease from reliable sources, because you are the one that has the greatest vested interest. 

Abbie: Yes. Dr. Kobayashi, I want to thank you so much for being our guest today. Your insights on immune dysregulation and how we understand immunodeficiency as part of a broader spectrum were incredibly valuable. And I think our listeners will really enjoy hearing about that. I know that I've frequently received those questions that I mentioned like, how can I have immune deficiency and still have autoimmune disease? I know because of that, this conversation will resonate with so many of our listeners living with these conditions daily. And we really look forward to working with you and continuing this conversation at another time. 

Dr. Kobayashi: Thank you.

Abbie: Thank you again for joining us today. Additional information regarding this podcast can be found on our website at www.igliving.com. If you have a question that was not answered, please contact me at acornet@igliving.com. 

Look for the next IG Living podcast announcement on our website for the opportunity to submit your questions. 

IG Living Advocate is a copyright production of IG Living Magazine, published by FFF Enterprises, the only magazine for the immune globulin community, comprised of patients who suffer from chronic illness and their caregivers.