Brain mast cells link the immune system to anxiety-like behavior
Though I now understand a lot more about mast cells and their impact upon my body and mind, I find myself pondering those 40 something years that I was in the dark. It’s honestly a miracle that I’ve come as far as I have without more consequence.
It is my sincere hope that sharing this information will help others become more aware of the impacts that unstable mast cells and histamines can have on the body and mind.
I met an AMAZING young lady several months ago–and before you worry, I did ask permission to write this blog before I wrote it–and I’m grateful to have the opportunity to be able to share with all of you about this experience. I think it’s almost as valuable to all of you as it has been for me.
Why am I writing about her today, though? I didn’t realize until today that she isn’t just a kid with EDS who likes me because I like Taylor Swift and hanging out with her. She’s me. She’s me if I had the chance to go back and meet myself when I was 14. She’s me if my mom met a doctor who could have told me what was going on with my body. She’s me if I had a support group to attend and doctors to assist me and parents who knew how to fight for my accommodations at school.
You would never guess if you met me today that when I was 14, I was shy. I was quiet. I wasn’t at all sure who I was going to be. I didn’t know at all where I was going in life.
I remember being in middle school and the pain that went along with it. My body hurt every single day. It hurt a lot more that kids thought I was faking it. It hurt more when they told me in gym class that I was “lucky” I’d sprained another joint. It hurt in high school when they laughed about me needing to leave class early because the elevator was so far away from all the classrooms that I needed extra time to get there. They pushed their way past me in in my wheelchair during a fire drill to such a point I wondered if I would die in the event of an actual fire while all the mean girls escaped with their lip gloss still intact. I had a few really close friends I loved more than anything–and a lot of kids who would never understand no matter how many times I tried to explain.
I never knew an adult with my condition when I was 14. I didn’t even know what my condition was–but I certainly didn’t know how I was ever going to escape from those hallways with my pride still intact. I was afraid to be there. I wish I had known some. I wish I’d met someone. I wish they’d come up to me to talk to me about Taylor Swift and tell me the mean girls read their blog now (because they do).
This young woman is smart, funny, and beautiful–in order of importance. She is in the time of life when I was most struggling. She is in the time of life when I found I most needed words from others.
It’s funny, though, because I’m 27 now. I’m an adult. I’ve known what’s “going on with my body” for more than two years and the first time her mom told me that talking to me was enjoyable for her, I think it helped me more than it helped her. I think it was better for me that I had someone to walk with me at an EDS Awareness Walk who wanted to talk about Taylor Swift and puppies when my fiance couldn’t be there with me. Nothing I have accomplished in my life matters more to me than making a difference in the lives of young people who have EDS–and what I have found is that they actually make an even bigger difference in my life than I could ever make in theirs.
I hope she remembers for the rest of her days, even when EDS and its related conditions are dictating what she can do in a given day or even what she can physically do in a given lifetime, it doesn’t dictate for a second what she can do with her heart and her mind with every day on this earth. I hope she knows that sharing a smile and a laugh with her made my day and my life better. I hope she knows that she was the person I most wanted to see today–and that I was saving some Taylor videos on my phone just for her. I hope she finds her voice the same way I did but that I will be here to be a sounding board every time she needs one while she’s still growing up.
Someone said today, “middle school is hard enough without all of this.” It was the truest and most painful thing I had heard in a long time. I would never wish EDS on every person who knows me, but I will use all of the words I can write to help them understand. It’s not as effective on 10-18 year olds, but that’s why we have to find our younger selves and love them the way we needed someone to love on us. We need to support them the way we needed someone to support us. We need to let them speak and write and LISTEN to them as much as they need.
Then, when you hear later that the time you spent made a difference in their lives, I promise you, it will help you even more than it helped them. Finding your young self is rewarding. Showing your young self shared interests and friendship is some of the best medicine there is.
I haven’t written here for a while because truthfully I haven’t been up to it. I’ve always been someone who finds a lot of comfort in working hard and my doctors forced me to take a medical leave because we can’t control my pain. So, I’m on week two of a four week leave from my job. Now, instead of spending my days working and contributing to my office—I’m spending my days on the couch and taking extra naps with my dog. This gives me a lot of time to think and ponder—and I’ll be getting to those ponderings VERY SOON. But first,
Taylor Swift (I know, I have a one track mind, but hear me out) has a lyric that says “Wish you could go back and tell yourself what you know now.” It’s about thinking you’re in love when you’re in high school and the decisions you make around that love.
In my life, though, it’s more about wishing I could go back and scream into my own ears “ASK YOUR DOCTOR ABOUT EDS; TELL HIM THIS IS WHAT YOU HAVE. TELL HIM NOT TO CUT YOU OPEN UNTIL HE FIGURES THIS OUT. MAKE HIM STOP.”
Today, I had a doctor’s appointment, so I had to leave to drive to see my doctor to discuss things. The specifics of what happened aren’t important. What is important, though, is when we got to a part of our discussion when he said, “This is something that should have been done for you at least fifteen years ago. This is a series of tests that should have been done for someone with this sort of condition at least by your early teens. We would have known then. We could have done more.”
It’s been a little over two years since my diagnosis and this is probably the fifth or sixth time a doctor has been this blunt about the nature of a need my body has. Not understanding what was happening in my body for so many years means that we did not get the treatments I could have had. We did not see the doctors I could have seen. My mother did not know. She could not ask the questions. She could not help. I call these situations the “Should’ves, Would’ves, but Didn’ts.”
It goes something like this: We should have (should’ve) done <insert medical concept here> for you. It would have (would’ve) allowed us to <insert medical result here>. Unfortunately, we did not (didn’t) know of your diagnosis at the time, so we must now follow through with <insert updated version of medical concept here>. Voila! A formula for Should’ves, Would’ves, but Didn’ts!
I don’t know when you get over them, but I do know they continue to affect EDS patients for a long time. I do know they play a critical role in the damage to our bodies for longer than we like to admit.
I’m not a doctor. I can’t give medical advice. I won’t give medical advice.
I will tell you these things, however.
If you are NOT in the EDS community:
If you have ever wondered why it is that I speak and write and share so much about my health—it is because all I seek to do every single day is prevent another 27 year old from wondering what her life would be like if those tests had been run when she was 12.
Sometimes we need extra support at doctor’s and after them. If we ask for you to join us, please do. Other times, we really prefer to go alone. Please respect that.ves
If you are in the EDS community:
It’s okay to need time to process that you DIDN’T have those things done for you before. I am a FIRM BELIEVER in crying in the car after the doctor. I BLAST Swift and cry on the road from Madison to Whitewater so often you’ve probably heard me at some point on I-90.
Once you have a diagnosis, you have a responsibility to work for the answers you need. You have to learn to be your own advocate. You can’t expect doctors to just KNOW what you need if you don’t tell them.
The best way to prevent future “Should’ves, Would’ves, but Didn’ts” is to get educated. EDS usually is like this fun game that includes a bunch more diagnoses. They don’t always have the time to teach you everything in a single appointment. Educate yourself. Seek out resources. Speak with others in the community. ASK QUESTIONS.
Just like Taylor wished and couldn’t, you also can’t go back and tell yourself what you know now. You can make sure you’re seeking out every single opportunity in your present. Come to our support groups. Read our blogs. Become our friends. Ask us questions. Let us help you. We promise that’s what we want to do. We promise we won’t judge your situation—ever.
Hey everyone, it’s Sam again! I reached out to you guys via the Facebook community a few weeks ago and got a few requests for information on mast cells and MCAS. I personally don’t have MCAS, so it’s not something I research as intently, but I LOVE immunology and thought this would be a really fun thing to talk about.
Immunology can be a scary subject, even for biologists. It’s very detail-oriented, there are a LOT of things going on, and the scientific community still doesn’t understand a lot about how the players in the immune system work. We do know that the immune system interacts with other parts of the body, like the nervous system (neuroimmunology recently crossed my radar and I’m enthralled!), to cause some interesting effects, so immunology is becoming a hotter and hotter topic for research.
The big player in MCAS is, as the name implies, the mast cell. To understand MCAS, we need to break down what mast cells are and what they do.
These guys are mast cells:
They have a bunch of receptors on their cell surface that let them talk to other cells in the body and receive input from both other cells and the environment they’re in. All those dark purple circles you see in the image above are called granules. Many different cell types have granules in them, and they can hold different types of chemicals (often called cytokines or chemokines) depending on what the cell needs to do. Mast cells usually have granules full of histamine, but they can also hold enzymes that chop up proteins (proteases), neurotransmitters like serotonin, and a bunch of other types of chemical messengers and enzymes. Histamine is the compound we usually talk about when discussing mast cells and allergy, and it makes a lot of different things happen depending on where it’s released.
So….what exactly does histamine do? There are 4 main histamine receptors in the body, and when they’re activated, each one can cause different things to happen. Some are more common in different parts of the body, which is why histamine can trigger different kinds of reactions. From typical seasonal allergy-type reactions or skin irritation to GI symptoms, to nervous system effects like nausea and vertigo, and even anaphylaxis, histamine can trigger a wide range of symptoms which is why MCAS can be difficult to diagnose. Many signs can be relatively benign or nonspecific, but when typical allergy testing comes up negative, it may be time to investigate MCAS.
Keep in mind that the other chemicals mast cells release can cause other things to happen, too. It’s not all about histamine!
So how are mast cells activated? Mast cells have cell surface receptors that can bind allergens, specific classes of antibodies, and signals sent out by other immune cells. When activated, mast cells release their granules, which then break open and release their contents into the local environment and trigger other events to happen.
It isn’t fully understood why mast cells don’t behave normally in MCAS. It’s important to note that MCAS is not the same as mastocytosis, which is characterized by an abnormally high number of mast cells; in mast cell activation syndrome, mast cells are activated too easily and are releasing their contents in situations they typically wouldn’t. Some environmental triggers can stimulate mast cells, like excessive heat or cold, sunlight, mechanical irritation, and chemicals or products on skin. There’s an observed correlation between MCAS, POTS, and EDS that isn’t fully understood.
MCAS is a very involved disorder, and it would take significantly more than just one post to do it justice. Hopefully this quick overview was helpful! Don’t hesitate to reach out to me via the EDS, Wisconsin Inc. contact page, or on the EDS & Joint Hypermobility Wisconsin Facebook page if you have anything in particular you’d like for me to discuss in detail.
*Disclaimer: I am not a physician, and I am not qualified to give anyone advice about their medical condition. All posts written by me are strictly meant to inform and empower patients and medical professionals alike, with the information they can use to better communicate with each other. If you have questions about your condition, please ask your doctor.
Mast cell secretory granules: armed for battle. Wernersson S, Pejler G. 2014. Nature Reviews Immunology. 14: 478-494.
Mast cell activation syndrome: a review. Frieri M, Patel R, Celestin J. 2012. Current Allergy and Asthma Reports. 13(1): 27-32.
Mast cell activation syndromes. Akin C. 2017. Allergy and Clinical Immunology. 140(2): 349-355.
Misbehaving Mast Cells in POTS and Other Forms of Dysautonomia – https://vimeo.com/246313546 (I didn’t actually watch this, but thought it would be a great resource!)
Prevention Genetics and Advanced Tele-Genetic Counseling (ATGC) joined us at our latest event, Meagan’s Walk for EDS Awareness and Suicide Prevention and shared in announcing our amazing news.
EDS Wisconsin, Inc. has worked to make genetic testing more accessible, through telephone counseling and self-administered testing. This can eliminate the long wait, often years, many people face trying to get an appointment and testing with a geneticist.
I’ve written in the blog a few times about my love of Taylor Swift, so if you caught the context of my title as a song lyric, props to you. In this case, you also hopefully caught that we’re playing with today’s holiday.
It’s Mother’s Day and that means we are celebrating all things mom. Here at EDS Wisconsin, many of us have shared and sought feedback about what our moms were like, what it means to be a mom to an EDS kid, and what Mother’s Day means to us. I asked my mom, Janell Armstrong, a few questions this morning and if I could write about her in my blog—mostly because I remember vividly what dealing with my health was like as a child and now that I’m 27, I wanted to hear what that was like from her perspective. So, I asked my mom the hardest part of raising a child who was clearly ill with SOMETHING but un-diagnosed. Then, I asked my mom the hardest part about having a child get diagnosed with an incurable condition at 25—and changing all of those things that happened in my youth.
My diagnosis story is LONG and I’ve written about it a few times in this blog. The first time I dislocated a joint fully, I was only 12 years old. I had no idea what a dislocation was, but I did know that my kneecap was on the back of my leg—and I was thoroughly convinced it would stay there forever. I don’t know if I’ve ever
My Mom and Stepdad, Dave
, to this day, screamed the way I did that day or shed as many tears. It was an incredibly hot summer day and the knee immobilizer was AWFUL for a child, not to mention that even though I always thought crutches looked “fun,” they were actually really awful to use and I had no clue how to use them. That really didn’t seem like a big deal, though. Kids get hurt. You all know this. If you have a kid who didn’t end up on crutches at least once in their childhood, consider yourself.
The problem is, it didn’t stop. It never stopped. The dislocations got more frequent in that knee as I got older. I would hurt other joints, too and cry until my mom would take me to the emergency room—and I’m realizing now that I’m four paragraphs in that I failed to mention that my mother, superhero that she is, was raising four kids all by herself. I begged my mother not to make me go to school. I begged her not to make me go to gym class. I would cry for actual hours while she put ice packs on various parts of my body.
My mom did a lot of things for me most parents don’t have to do—and sometimes she took heat for it. I had a predetermined number of days off school I could take off every month because sometimes I just couldn’t handle school. There were times I sprained my wrist so badly I couldn’t write my own homework even though I came up with all the answers myself—and when I asked the teacher if that was okay, she told me, in front of the entire class, that she would have found a way to write the homework herself, so she was going to take a few points off. I have a feeling she and my mom talked about those points because I never lost them. I was a straight-A student and I wanted teachers to like me, so when they didn’t because I couldn’t do something, it hurt even more than my body did.
Then, there were the doctors. The first time a doctor told me I only hurt because I was fat, I was six years old. The same doctor told my sister blue eye shadow was “slutty” when she was 10, so I’m not quite sure where she went to medical school…but anyway now I’m WAY off topic…hopefully you’re laughing. By the time the dislocations were happening every day, multiple times a day, I was tumbling down stairs—a LOT. My mom told me this morning that what she felt more than anything with doctors when I was a kid was helplessness. She felt helpless to get answers, helpless to fix me, and helpless to make her child better. She wrote, “You SO want to believe that the next doctor will be able to fix it. I had a tendency to believe them because they are supposed to know more than you! And if this, this, and this happens, it will all be over and your child will be all fixed. It’s a little better now with online resources, but honestly, when you were going through all of it, I didn’t really know where to go besides the doctor to get answers.”
I never heard my mom say until today that she thought the same things I did. “This, this, and this and your child will be all fixed” is neither scientific nor eloquent—but it is what moms of an un-diagnosed child desperately want. It’s what those children want even more. I felt guilt over making my mom take me to the doctor over and over again only to be told they didn’t know or I was fine or this surgery would fix it all—and then it never did.
Here’s how I remember it, though, when the doctors didn’t help me enough, my mom didn’t stop. She never, ever stopped. That lesson stuck with me. I didn’t stop either. When I was 23, I saw another doctor who didn’t help me enough, so I didn’t go back. It happened again when I was 24. Then, when I was 25, a doctor FINALLY told me why I was in so much pain, why I was so sick, why I was the way I was—and suddenly every single trip to every single doctor all those hours away was worth it, because we never gave up.
My mom’s response to my diagnosis question hit me harder than I thought it would, because I wish she didn’t have to feel how she did or does. She explained that it killed her a bit when she found out. She wrote that she questioned every decision she ever made regarding my care. She wrote about guilt for not doing a better job and not pushing doctors. She wrote about the worse guilt about those moments when she doubted her own child’s pain.
So, this is for my own mom—and for any other mom who couldn’t get their child diagnosed until adulthood. These words are my words for you, my thoughts for you, my love letter to the “mama” who made me strong enough to live through EDS:
You are not a doctor. You are taught to trust doctors with your lives. A doctor brought me into this world and you trusted them to help you care for me every step of my life. You pushed. You kept pushing—and you gave me the tools to keep pushing once I left the nest. I am my own greatest advocate because I learned from watching you.
I doubted my own pain more than you ever could or ever will. I thought for sure it was all in my head. There was no way doctors could possibly go thirteen years and find nothing if I was actually ill, right? You don’t have to carry guilt for wondering about something I couldn’t help but wonder myself.
You didn’t make me sick. You made me strong. You gave me all of the wonderful and beautiful things about myself and without EDS, I probably wouldn’t have been able to make these traits what they are today. I will work harder to remind you of that for the rest of my days with you.
Watching your child in pain and not being able to help is probably worse than being in pain yourself. You’ve told me so many times that you wish you could just take my pain. I know you mean that. I know you would ACTUALLY do that for me. I know that you would give up walking yourself if it meant I could keep walking. That’s how much you love me. That’s how much you have always loved me. (And some days, I’m selfish enough to let you.)
My mom’s point about not having resources to help her is exactly the reason I do what I do. She is the reason I speak publicly when I can. She is the reason I write this blog and share my story on social media, because I promise you there is a mother out there somewhere with a daughter crying from her pain and the mother does not know what to do—and if I can help one more mother not have to question the decisions she made because she read OUR story (mine AND my mom’s), I will keep doing it for as long as I can.
To all of the mothers raising children with chronic illnesses or who have chronic illnesses themselves, you are strong and brave and wonderful and even though you deserve recognition every day, you especially deserve it today. Happy Mother’s Day.
FOR IMMEDIATE RELEASE: 04/23/2018 Angela Braun (715) 370-1736
Meagan’s HOPE Memorial Walk Ehlers Danlos Syndromes Awareness & Suicide Prevention
Wausau, WI: EDS Wisconsin, Inc., EDS Wellness, and the Braun Family are hosting the First Annual Meagan’s HOPE Memorial Walk for EDS Awareness & Suicide Prevention at Wausau’s Oak Island on Saturday, May 5, 2018. Special Guests in attendance include Geneticist Dr. Juan Dong and Jessica Reed of PreventionGenetics, Pain Specialist Linda S. Bluestein, M.D., Executive Director Kendra N Myles of EDS Wellness, Executive Director John Ferman of EDS Awareness, and the Co-Founder of Advanced Tele-Genetic Counseling. A special announcement will be made at 1:00 pm followed by a brief Q & A session and a one mile Walk.
Ehlers Danlos syndromes (EDS) are a group of heritable connective tissue disorders that impact individuals of all ages & genders. Frequently misdiagnosed as Fibromyalgia, Chronic Fatigue Syndrome, or various psychosomatic illnesses, EDS affects nearly every body system since connective tissue is what holds the body together like glue. Many of those who have EDS experience daily pain, excessive fatigue, increased bleeding, and they have overly flexible joints which can lead to joint dislocations, as well as many other seemingly unrelated symptoms. Support and resources for medical professionals and patients affected by EDS remains limited. Sadly, EDS frequently goes undiagnosed for many years causing both patients and medical professionals needless suffering. Early diagnosis is validating and empowering for patients, their loved ones and medical professionals! Diagnosis enables proper treatment strategies and fewer unnecessary medical visits.
Born December 12, 1987, Meagan Rae Braun was a kind, caring, loving individual with a most beautiful, gentle soul. She grew up in Medford, WI and most recently resided in Weston. Meagan was an outstanding mother of two young children and truly enjoyed helping others while continually seeking knowledge, truth, peace and harmony. Even so, behind her beautiful smile, Meagan suffered with multisystemic illnesses including EDS, hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS), allergies and sensitivities, and more. Frustrated with limited treatment options for her health, in addition to battling postpartum depression, Meagan lost all hope resulting in her death from suicide on April 24th, 2017. The Walk is being held in honor of Meagan’s gracious spirit.
The Mission of the not-for-profit organization EDS Wisconsin is to provide support and resources to Wisconsin patients and medical professionals about Ehlers-Danlos Syndromes and related conditions via education and research. Together with the Braun Family and the prestigious national 501(c)3 organization EDS Wellness, this Walk is an opportunity to increase awareness, support, resources, and education for those affected by EDS and suicide. There will be raffle prizes, t-shirts and balloons for participants.
This event is proudly supported and sponsored by Wisconsin Integrative Pain Specialists, Linda S Bluestein, M.D., Prevention Genetics, The Caring Tree Children’s Counseling Center, Advanced Tele Genetic Counseling (ATGC), Concrete Creations of Wisconsin, Inc., EDS Awareness, Mariah Liisa Design, LLC, and Tools of Marketing, Inc.
Please join us at Wausau’s Oak Island on Saturday, May 5, 2018 at 1:00 pm! For more information on these conditions and to pre-register go to www.EDSWI.org
Hey everyone! Before I dig into some science, I’d like to take a second to introduce myself. My name is Sam and I’m a veterinary medicine student at UW-Madison (I also have a BS in microbiology and genetics), science enthusiast, and fellow zebra. I’m very passionate about science communications and making difficult-to-understand concepts more accessible to people with non-scientific backgrounds. When it comes to EDS, I strongly believe that understanding the biology behind the disease empowers patients and allows them to ask their doctors the right questions to get proper care. Additionally, I want to provide resources for medical professionals so they may learn to care for patients with diseases they may not be familiar with – I’ll be leaving citations at the end of each post for this purpose. I’m exceedingly grateful to EDS WI, Inc. for giving me this opportunity. As this is my first post, I thought it would be fitting to discuss what collagen is, why it’s so important, and why it can cause different manifestations amongst EDS subtypes.
I also want to take a second and clarify a critical point: genes set the template for the body to make proteins, and proteins are the workhorses of the body. Proteins are what actually “do” things and carry out a function. If you have bad blueprints – mutated genes – your body doesn’t make a normal protein. Sometimes, like in the case of EDS, these abnormal proteins can have noticeable effects in the body. Proteins are made in different parts of the body at different levels due to a mechanism called “gene expression.” This is why you have nails at the end of your fingers instead of on your forehead!
Most of us know that collagen is a foundational protein found throughout the body and that it’s essentially a “building block” for different structures, but did you know there have been 29 different collagen proteins identified to date? Some of them are more common or have a bigger impact on the body when they don’t work properly compared to others. The first five types are perhaps the most important and well-understood:
Type I collagen is by far the most common in the body and makes up parts of your skin, tendons and ligaments, blood vessels, and bones. It often works in partnerships with other kinds of collagen.
Type II is a huge component of cartilage.
Types III, IV, and V help anchor cells to each other (using what’s called a “reticular fiber”) and to other types of tissue, in some cases forming barriers called “basement membranes” underneath layers of cells. These collagen types are important for microscopic, cell-to-cell activity.
As you can see, each collagen type has its own job to do, which is why there are different subtypes of EDS that can be described by which collagen protein isn’t working. For example, mutations in type III collagen can cause vEDS. This makes sense because the fibers type III makes are critical for forming the architecture of the heart and major blood vessels and give them the ability to stretch and accommodate changing amounts of blood.
Some types of EDS don’t have collagen mutations at all! In these cases, proteins in the body that have to work with or use collagen are mutated and lose their ability to do their jobs. Essentially, the body’s collagen is fine but it can’t be used properly. In periodontal EDS, C1R, a gene involved in a specific part of the immune system, is mutated and collagen is normal. However, the culprit protein uses collagen to make itself. When C1R can’t do its job, the mouth ends up becoming very inflamed, which can cause dental problems.
We’ve all heard the metaphor that likens collagen in the body to building a house. If you have a crummy foundation – mutated collagen – the house will probably wear out more quickly than it should. To add some nuance to the metaphor, imagine collagen is the wood you use to build your house. It forms the walls, the roof, the floor, and maybe some structures inside like cabinets and doors. All in all, pretty important structures to have in a place to live, right? If all of your wood is bad, it’s going to have pretty serious effects throughout the house. Maybe only the wood you use for your roof is bad – your walls will still stand, but maybe some rain leaks in through the ceiling. Maybe your carpenters don’t know how to use the perfectly fine wood you bought, and that’s the reason your floor caves in.
Thinking about collagen this way can be a really helpful tool for understanding why different types of EDS exist. There isn’t just one type of EDS, just as there isn’t one purpose for the wood you buy to build a house. Medically, you don’t treat similarly or lump together patients with different types of EDS, much like you don’t have your carpenter install your plumbing.
*Disclaimer: I am not a physician, and I am not qualified to give anyone advice about their medical condition. All posts written by me are strictly meant to inform and empower patients and medical professionals alike, with information they can use to better communicate with each other. If you have questions about your condition, please ask your doctor.
Preparation and characterization of the different types of collagen. Miller EJ, Rhodes RK. 1982. Methods Enzymol. 82 Pt A 33-64.
Collagen: a overview. Miller EJ, Gay S. 1982. Methods Enzymol. 82: 3-32.
Elastic and Collagenous Networks in Vascular Diseases. Arteaga-Solis E, Gayraud B, Ramirez F. 2011. Cell Struct. 25(2):69-72.
Periodontal Ehlers-Danlos Syndrome is caused by mutations in C1R and C1S, which encode subcomponents C1r and C1s of complement. Kapferer-Seebacher I, Pepin M, Werner R, et al. 2016. AJHG. 99(5):1005-1014.