Conference Coverage

Autoantibody Profiles and Prediction of Myositis Phenotype and Disease Course

Julie Paik, MD, MHS

​​​​​​In this episode, Julie Paik, MD, MHS, discusses autoantibody profiles and prediction of myositis phenotype and disease course, including how the prediction of myositis phenotype and disease course impact clinical practice, and gaps in the research. Dr Paik presented on this topic at the Congress of Clinical Rheumatology (CCR) East 2022 meeting.

Julie Paik, MD, MHS, is the director of clinical trials at Johns Hopkins Myositis Center and an assistant professor of medicine in the division of rheumatology at Johns Hopkins University School of Medicine (Baltimore, MD).

For more information about CCR East and West 2022, visit



Jessica Bard: Hello, everyone. And welcome to another installment of Podcast 360, your go-to resource for medical news and clinical updates. I'm your moderator, Jessica Bard, with Consultant 360 Specialty Network. Myositis affects about 50,000 people in the United States, according to the Johns Hopkins Myositis Center. Dr Julie Paik, it's here to speak with us today about her session at CCR-EAST 2022. Can autoantibody profiles predict myositis phenotype and disease course? Dr Paik is the director of clinical trials at Johns Hopkins Myositis Center and an assistant professor of medicine in the division of rheumatology at Johns Hopkins University School of Medicine in Baltimore, Maryland. Thank you for joining us today, Dr Paik, can you please provide us with an overview of your session?

Dr Julie Paik: Yes, so the overview of the talk, basically, I highlighted the different types of myositis-specific autoantibodies and myositis-associated autoantibodies, so MSAs or MAAs, in the world of myositis, so to speak. And I tried to break it down because there are so many myositis autoantibodies by different subgroups of myositis. So, for example, what are the autoantibodies in dermatomyositis? What are the autoantibodies that we should think about in this entity of antisynthetase syndrome? What are the autoantibodies that we need to think about in immune-mediated necrotizing myopathy? And then lastly, I also discussed the overlap between myositis patients because those are the patients where we usually see myositis-associated autoantibodies being positive. And then, the MSAs again, are usually seeing more specifically in those with dermatomyositis, polymyositis, or antisynthetase syndrome. So, I divided it like that, because I think it's a little bit easier to break down in the clinical context as well.

Jessica Bard: Sure. That makes sense. How do the prediction of myositis phenotype and disease course impact clinical practice?

Dr Julie Paik: So, yes, I got a lot of questions about this during the conference as well. And in my talk, what I highlighted was that patients with myositis, once they're positive for an autoantibody, usually that does not track with disease course. If the titer is really high or goes down after treatment, it doesn't necessarily mean that patient is doing extremely well and will not have a flare or things like this. So basically, once you're positive, you're positive. The only exception that I highlighted during my talk is that in the patients who have an immune-mediated necrotizing myopathy who are HMGCR positive, those patients, they have been shown a disease marker of muscle weakness is the CK or creatinine kinase. Those levels track with the titers of HMGCR to the myositis-specific autoantibody. And so, that is the only evidence currently that shows it can potentially track with disease course specifically.

And I gave an example that if I have a patient who's extremely high titer HMGCR antibodies, then I know that they're probably going to be extremely weak, which is usually the case. And they usually have high CKs. And sometimes I even recheck it, if they're not responding, to see if maybe even the tighter had come down or is it still extremely high. Of course, the autoantibody level that we check there is a ceiling to it, so it's not perfect, but sometimes it can be helpful. So that's one exception that immune-mediated necrotizing myopathy, specifically HMGCR autoantibodies. I explained the reason why some other examples of why in dermatitis or in antisynthetase syndrome, the autoantibodies, it doesn't really track with the disease. So for the one example I gave is there has been reports of patients with antisynthetase syndrome and those patients can get lung disease and even severe lung disease requiring a lung transplant.

And they have checked autoantibody titers after lung transplant and they're still high. They don't go down just because you got a new lung and things like this. And they're doing well on an immunosuppression with the new lung, but that's a good example of anti-Jo1, which is a classic, very specific autoantibody for antisynthetase syndrome where it does track with disease activity or course. And then, the other example I gave is in multiple trials, including the one that I was a principal investigator on of a JAK inhibitor in refractory dermatitis. We looked across autoantibody titers in patients with dermatitis pre and post-treatment and they were not different. And there's data to support that as well in the literature. So I really think again, the HMGCR antibody story and tracking with CK or creatinine kinase levels is one exception and can track with disease activity.

Jessica Bard: think that's a great segue into our next topic, knowledge gaps. Can you explain some knowledge gaps in this area?

Dr Julie Paik: Yeah, I think the knowledge gaps are that there are so many different autoantibodies and it's still being understood. I mean, the key take-home point from my talk was these autoantibodies are extremely useful for diagnosis and prognosis because these patients have distinct clinical phenotypes that tightly associate with the presence of an autoantibody. So, for example, if someone is NXP-2 positive, then I know they will have dermatomyositis. They probably will have calcinosis. If they're a TIF1 gamma positive, I know that they tend to get more refractory skin disease dermatitis and they tend not to have other organ involvement like interstitial lung disease. And there's that type linked with a potential malignancy that's driving TIF1 gamma. So these things are all based on multiple important prospective cohort studies that have shown this kind of associations that are important and then can guide the clinician program myositis panel.

But again, there's so many other myositis autoantibodies where we don't know that. So for example, and that's the knowledge gap where if someone has a very rare synthetase. For example, like anti-Ks or OJ or EJ. I know these names sound a little ... They're so rare that we don't even know exactly what their clinical phenotype is. We say, "Oh, they're probably going to have myositis and interstitial lung disease most commonly." But it's so rare that we haven't studied it in more detail. We don't know if there's potentially a cancer risk in those type of patients. I think this would be the major knowledge gaps. And then, in regards to understanding all the different types of clinical phenotypes associated with these myositis autoantibodies, some of them we know very well and some of them, we don't.

The other knowledge gap would be that there are times, and I don't know if I really highlighted this in the talk, but there are times when we have patients with biopsy-proven dermatomyositis, like skin biopsy and muscle biopsy. And we check a myositis panel to look for these autoantibodies, but they're negative. And so, there are still many autoantibodies probably in the future that need to be discovered. And I think that is the major knowledge research gap, which hopefully will be further elucidated through prospective cohort studies and things like this.

Jessica Bard: Again, great segue into the next topic. What is next for research on this topic?

Dr Julie Paik: Yes. At our myositis center, we have a wonderful multidisciplinary clinic and we have an amazing translational group that we work with led by Dr Livia Casciola-Rosen. And partnering with these type of translational experts help us hopefully to identify new autoantibodies and better understand those people where we can't find an autoantibody, but we know there has to be one. And so, sometimes, actually when we order the myositis panel and we send it out and we get a result and we know they definitely have dermatitis or immune-mediated necrotizing myopathy, but it says unidentified autoantibody. You're like, "Okay, well, what is that unidentified autoantibody?" So, and then the patients give me a real-world example and be like, "Well, I know I have the disease and everywhere I read on the internet says that I should have a myositis autoantibody with my disease, but how come I don't have one?" And I'm like, "Well, something unidentified," so there's definitely that big knowledge gap where future ... And there's always going to be new discoveries in that sense.

Dr Julie Paik: And I think that's one of the biggest research area for that in that topic area. The other thing would be to hopefully have more biomarkers in addition to the myositis autoantibodies to track with disease activity. Because right now it's really a lot based on clinical parameters. And sometimes, it can be hard if someone has chronic myositis, like the CK level or the creatinine kinase level, it may be normal or just mildly elevated. But the patient's like "I'm extremely weak" and they have chronic myositis and they're already on immunosuppressant. We're not going to be able to really get to the ... Determine if they really have active disease. And so, if there are other biomarkers in the blood that we can check along with clinical assessments, I think that would be also very helpful.

Jessica Bard: Now I know that you already mentioned a few, but if you could just sum it all up the overall take-home messages from your session.

Dr Julie Paik: Yes. I think the overall take-home message is basically first and foremost is that these myositis autoantibodies are tightly linked to phenotypic expression or in layman's terms, basically that it's associated with a distinct clinical presentation, which can guide rheumatologists and even maybe a non-rheumatologists or anybody treating myositis for that matter to get an idea of their prognosis and what other organ manifestations they may have. So for example, if someone is Jo-1 positive, which is anti-synthetase, then I know that most likely they will develop interstitial lung disease. So that's something that I can look out for in terms of screening if they don't have it at the first time I meet them, but I should be aware of it. And I should also inform the patient to be aware of it over time. Like if you develop shortness of breath or things like this.

And so, that prompts the provider to consider doing baseline pulmonary function tests and CT scan. So number one is really that it is associated. These autoantibodies are associated with distinct clinical phenotypes that help them further guide us to make clinical decisions and also educate our patients as well. And then, second would be not to be, how do we say, not to be overwhelmed by the different autoantibodies. But try to at least for the provider, once you get them back, really think about what subgroup of myositis they belong to and then make practical decisions around that. I think that's also ... Just not to be overwhelmed with it, I think. Sometimes because there are just so many, I think it can become overwhelming.

Jessica Bard: Is there anything else that you'd like to add today?

Dr Julie Paik: Yeah, so I think the dream for myositis experts and myositis specialists is that one day we can actually have a treatment algorithm that specifically focuses on those who are like TIF1 gamma positive or Jo-1 positive and just tailor the therapy to those who have that specific autoantibody because we know that autoantibody, it's so specific with a particular clinical presentation that I think I would love to potentially have some type of trial or treatment algorithm that's specific to that autoantibody. So I can tell the patient, "We know if you're positive for this autoantibody then X, Y, and Z will work extremely well for you." And I think that would be the dream of mine and I'm sure many of others, but over time, hopefully, because it's a rare disease, we can do a trial like that in the future.

Jessica Bard: Well, thank you so much for your work on this topic, and thanks for taking the time to speak with us. We appreciate it.

Dr Julie Paik: Yes, absolutely. Thank you so much for having me. It was really nice to speak to you and it was really fun.

Jessica Bard: Thank you