The Scleroderma Chronicles: Coming Full Circle

Systemic Sclerosis is a rare, chronic, progressive, and incurable autoimmune disease that is included in the family of rheumatic conditions. It is characterized by blood vessel damage and the scarring and thickening of skin due to excessive collagen production (fibrosis). The internal organs can also be damaged by inflammation and scarring: the digestive tract, heart, kidneys, and lungs.

There are two main types of systemic sclerosis: diffuse and limited.

I was diagnosed with limited systemic sclerosis 6 years ago.

Hannah: Do you like my circle?

The Circle Starts: In high school I developed a mystery illness that involved intense itching, lots of rashes, sensitivity to sunlight, and swollen digits. I was a mess. It went on for a few years and then the worse of the symptoms faded away.

First Quarter Circle: In my mid twenties I was a researcher working on a scleroderma project for the Division of Rheumatology at the University of Colorado Health Sciences Center in Denver, Colorado. The principal investigator that I worked for was interested in isolating the targets of the autoantibodies that scleroderma patients made; if we found the actual proteins that the antibodies characteristic of this autoimmune rheumatic disease were targeting we would be closer to understanding what they did, and eventually closer to understand the disease process of scleroderma. Let me be clear here: my boss, Dr. Angeline Douvas, was the brains of this little research outfit and I did most of the bench work.

One morning Angie had the hot idea that we should see what happened if we did an anti-nuclear antibody (ANA) test on the polytene chromosomes of the fruit fly Drosophila, a common lab experimental animal. We knew that the antibodies produced by the scleroderma patients were sticking to the chromosomes in the nucleus of cells… what would it look like if we checked this test on the chromosomes of fruit flies which were enormous structures that were easy to look at under the microscope?

After staining we could see that on the entire chromosome a few distinct bands were stained: only a few genes were targeted by the antibodies of the scleroderma patients. What was the function of the genes, and what were those proteins, the clear targets of the antibodies made by these scleroderma patients, doing? Something important that was linked to this disease that we call systemic sclerosis (scleroderma). How was all of that tied to the damaging fibrosis going on in these patients?

Here’s the other interesting conundrum that we kicked around: what changed in these genes/proteins that made them trigger the immune system to make antibodies? There are lots of things that can change genes and the proteins that they make. Things like radiation, chemicals, environmental triggers, viruses…

Hannah: Viruses?! The Kitten Mom and I spend all our time at home hiding from viruses!!!

Second Quarter Circle: Now in my 60s, and diagnosed as a scleroderma patient myself, I began writing letters to my congressman asking him to support the National Commission on Scleroderma and Fibrotic Diseases Act, a bill which would coordinate and organize resources to study the process that is involved in the formation of scar tissue in scleroderma and other diseases/conditions. Two summers ago I met with a representative of my congressman, Jason Crow, with other scleroderma patients to make our case. Scleroderma is special, I argued, because our antibodies are a tool that can be used to unpack the process of fibrosis. Representative Crow did support the bill.

Hannah: Now, are you ready for some really crazy stuff? Hang onto your catnip mice, this gets a little wild!!

Third Quarter Circle: It is 2020 and Covid-19 has arrived. Early on we learned that this is a serious virus that causes an extreme immune system response in some individuals that is life threatening. There is severe lung involvement, blood clots, scarred lungs, injured hearts, failing kidneys… this is no joke if you are already dealing with all of this, so I and other scleroderma patients are avoiding it like the plague and retreating to our online support groups even more than usual. We share observations and experiences in these forums, and it wasn’t very long before we started to notice that these severe Covid-19 cases seemed to be awfully similar to severe systemic sclerosis. We laughed about “Covid Toes” since dealing with blue fingers and toes is a daily struggle for us. Then the news reports about Covid-19 long-haulers started to emerge, and we all started to say to each other… wow… fatigue, brain fog, muscle/joint pains, lung and heart problems… sounds a lot like what we deal with… Then some people started to arrive in our support groups who were newly diagnosed scleroderma patients who were also Covid-19 long haulers. Now every week new people, shocked and frightened by their life-altering diagnosis of systemic sclerosis, are showing up in our forums. “Gee, there are a lot of new patients arriving,” someone wrote last week…

Unbelievable, right? I decided to hunt around online and quickly found that there were a number of reports about Covid-19 and systemic sclerosis. I discovered to my shock that people with severe Covid-19 disease do share a lot of documented clinical features with severely ill diffuse systemic sclerosis patients, and there is a connection between Covid-19 and rheumatic autoimmune diseases. When there was an article in the New York Times reporting that some Covid patients were developing autoimmune disease it caught my eye, so a little more work online found this nicely written overview by the Global Autoimmune Institute that listed specific research reports and the autoantibodies being discovered in Covid-19 patients and Covid-19 long-haulers. There in the reports are listed the same, exact autoantibodies that are the specific hallmarks of my two autoimmune diseases, systemic sclerosis and Sjogren’s Disease. 2020, shame on you. This is really, really bad, even for you.

All of a sudden it is really important to understand fibrotic diseases and how to reverse the damage caused by Covid-19.

Hannah: The Kitten Mom feels like she needs to do something about this!!

The Circle Closes: The genome sequencing service 23andMe has launched a genetic research study of systemic sclerosis patients. They are screening and accepting 1000 diagnosed patients who will donate their DNA for research into systemic sclerosis. I’m pretty sure that this effort to collect more information about the genes of systemic sclerosis patients is in part driven by the urgent need to deal with an emerging flood of new patients with fibrotic organ damage due to Covid-19 infections. Tonight I completed my application to submit my DNA to the study and to participate in all their additional data collection about my disease. Remember those few, distinct genes lit up on the fly chromosome? “Go get ’em, boys!” I muttered to myself as I clicked the submit button.

Today there were 225,558 new cases of Covid-19 in the US and 3,499 new deaths.

How many of the Covid-19 survivors will eventually be dealing with a chronic, progressive, and incurable autoimmune disease?

Wear your masks, people!!

Wednesday Afternoon Update: I’ve been accepted into the research program and they have already shipped my DNA collection kit to me. Hannah is so excited!!

Footnote: Did Angie and I find a protein using the scleroderma patients antibodies? Yep. We did.

Author: Midnight Knitter

I weave, knit and read in Aurora, Colorado where my garden lives. I have 2 sons, a knitting daughter-in-law, a grandson and two exceptionally spoiled kittens. In 2014 I was diagnosed with a serious rare autoimmune disease called systemic sclerosis along with Sjogren's Disease and fibromyalgia.

21 thoughts on “The Scleroderma Chronicles: Coming Full Circle”

    1. It kind of is. When I worked in medical research my lab manager once told me that research is the Art of Serendipitous Phenomenology; how crazy that the events of my life should connect like this?! The work was Angie’s all the way, I was absolutely the very junior partner of the team as her researcher. 🙂

  1. Great post! Kudos to you and Angie for solving a piece of the puzzle. I have seen stories about Covid long haulers but none that mentioned the connection to schleroderma. I am glad you are participating in the 23 and Me study and still moving our scientific knowledge forward. It will be interesting to see what they find out.

    1. That lab work continues to haunt me as the people with the worst form of systemic sclerosis, the diffuse form that has clinical similarities to Covid-19, is the one where people have antibodies to that protein we captured, SCL-70. I do not have those antibodies!! Angie was so intelligent that she was a little scary to work for; she went on to discover that people with lupus did not contract HIV and were virtually immune to AIDS.

  2. Fascinating read (and it brought back memories of college and working with Drosophila) . We hear a lot about Long COVID and to find this link is amazing. The implications of a possible genetic test to identify Long COVID susceptibility (and ultimately also identify those likely to develop severe COVID symptoms that have no other risk factors such as age) could have a huge effect on the impact of this virus.

    1. Ah… those Drosophila genetics lab were good times, huh! In my later years of teaching genetics to AP Bio students I used an online fly breeding lab. Instant results with no larva or escaped flies involved!!

      Imagine they could do a follow-up test of Covid-19 positive patients and then could aggressively intervene to prevent severe disease and/or development of autoimmune disease. That would be huge!! I was concerned about sending DNA because it might be used to predict susceptibility to autoimmune disease that might impact insurability, but finally decided that the possible benefits of reversing fibrotic injuries was too important to not do it. It would be even better if it could halt further damage, which would really help those people who have just received diagnoses of serious systemic autoimmune disease like lupus or systemic sclerosis (scleroderma).

      1. Anyone who’s studied genetics must have a certain amount of affection for Drosophila though the Dros Lab can be a smelly place …and yes I remember the escaped flies too!
        Very exciting research outcome possibilities with this and so nice to chat about the science on here. I’ve never met another knitting geneticist with an interest in auto immune disease before. I did my degree in genetics but didn’t pursue it as a career. I have had Crohns Disease since childhood, hence the interest.

      2. It was a little smelly, wasn’t it. Still, I did love it. 🙂 It is nice to chat about the science, thank you. My degree was in molecular biology and I first worked in an immunology lab before I got moved to rheumatology in Colorado. (My boss moved the whole lab to Colorado when he took over that department.) I love genetics and still do a lot of science reading. I guess we have a lot in common; I am a science geek through and through, I knit like I can’t live without it, and then there are the autoimmune diseases. Are you big into reading and gardening too? I’m pretty sure now that my autoimmune issues started when I was a teenager. I’m sorry about the Crohn’s as I know it is just a bear to manage. My GI pretty much rules my life too these days. Thank heavens for knitting!!

  3. Hi , I would to donate my DNA too for the research. Are they still accepting ? Could you please share more details about it?

    1. Here the link to the research study. I think that I remember that they were accepting 1,000 people into the initial study but then a lot of people just recently have also joined the study in the Facebook support groups that I hang out in. I had some trouble getting in as I opened an account and followed links only to arrive at a dead end several times. Suddenly it worked and I was in. Anyway, good luck to you and I am sorry that you also have systemic sclerosis.

      I got free DNA and ancestry results, but for the complete reports you have to pay some fees.

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