In August 2017 a wonderful EDS Awareness group Chronic Pain Partners hosted a webinar titled “Trypped Up by Tryptase: An Update on Tryptase Research at NIH.”
The speaker was Joshua Milner, M.D., Chief of the Allergy Lab (NIAID), Genetics and Pathogenesis at NIH (National Institute of Health). Usually the group posts recordings of the event for the general public, but in this case they only shared it with people who had registered to be part of the live webinar. Which thrilled me because I brain fogged the day of the webinar and missed it, but was able to watch it afterwards.
I can’t share the link to the video, but I CAN share my notes and thoughts! I hope they get him as a speaker again soon! I could really tell how much he cared about finding answers and making people feel better.
First and foremost, he said he gets asked a lot, but at this time his research group is NOT looking for new participants. He wished he could see everyone, but their resources are limited, and right now they want to focus on the cases they have. Taking on any more would be too overwhelming at this time. He hopes that their research sparks more interest in the area and stimulates more research down the road, but for now they are doing what they can.
However, he said it is part of his work to share their research findings, like he was doing with this webinar. He usually talks to live audiences rather than doing webinars, and travels the world to do so. And he said if you’re working with your local allergist and they want to know more, he’s more than happy to talk to them about what his lab has found.
The webinar focused on the findings of the recent paper that got a lot of attention in the EDS/hypermobile community when it came out, “Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number” which was spearheaded by Jonathan Lyons, a member of his research team. He clarified a lot about what the research really means, what the limitations are, some of the misinterpretations, and next steps. He referenced a few other articles as well, which I link to later in this post.
Tryptase and hereditary alpha tryptasemia background information
For the basics of what he covered in the first part of the webinar I recommend the NIH’s FAQ page: Hereditary Alpha Tryptasemia and Hereditary Alpha Tryptasemia Syndrome. You’ll find information about what tryptase is, the gene that makes it, and symptoms associated with the syndrome.
Most importantly, what he made very clear is that while they share many of the same symptoms, hereditary alpha tryptasemia syndrome IS NOT the same as mast cell activation syndrome. No study has yet been able to determine a causal relationship, and figuring out their exact relationship will require much more research. They see high tryptase levels often associated with mast cell activation and connective tissue disorders, but don’t yet know the mechanism behind the relationships.
Main limitations of the research so far
- possibilities of referral bias – people are sent to his lab because they are having issues, so it is hard for them to tell which issues are related and significant
- lots of chronic diseases have lots of share symptoms (like pain, functional GI issues, dysautonomia), so the question is are they just common symptoms or is there some sort of relationship?
- many people with one genetic disorder also have a second genetic disorder, so it can be hard to tell which symptoms are caused by which condition
- so you have to ask are these things related or just coincidences, and determining the mechanism of the disease or diseases needs lots of further study
What are the next steps?
- figuring out which symptoms come from mast cell release versus too much loose tryptase versus long term exposure to either
- involving more specialties to see what changes are being caused in cells, leading to connective tissue problems, cardiology, behavioral issues, etc.
- developing clinical trials to determine which treatments work and which don’t, because so far there is only anecdotal evidence from experienced practitioners
- finding a way to block alpha tryptase as a way to relieve symptoms (because almost 30% of the population functions just fine without any alpha tryptase gene at all – see Soto et al’s Genetic deficiency of human mast cell a-tryptase)
- developing a commercial version of the genetic alpha tryptase test they used in their study – said it should be available soon, but didn’t have an exact date, and also mentioned that he is not benefiting monetarily from the test
Other research mentioned in the webinar
- Fellinger et al: Clinic characteristics and risk profile of patients with elevated basal serum tryptase
- Abulkassim et al: Proteinase-activated receptor 2 is involved in the behavioural changes associated with sickness behaviour
- Posey et al: Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation
Other resources
- Lyons et al: Mendelian Inheritance Of Elevated Tryptase Associated With Atopy and Connective Tissue Abnormalities
- Mast Cell Activation Syndrome and Hypermobility
- Chronic Pain Partners Mast Cell Activation Syndrome Webinars