8 ms·

A Spanish teen’s genome may hold the secret to lupus

209 points by sohkamyung 4y ago

texaslonghorn5 4y ago
- changoplatanero 4y ago
  You should elaborate
  - AaronNewcomer 4y ago
    - lostcolony 4y ago
  - bigDinosaur 4y ago
    There's a not insignificant number of people who think they have lupus who, in reality, most likely do not, to the point where lupus has become something of a meme. It's characteristic of autoimmune disorders to be absolute pains to diagnose correctly as well as they often share symptoms with other disorders and entirely unrelated conditions (e.g. if you keep getting rashes that could be any number of autoimmune disorders or none at all, and more likely to be some environmental allergy than lupus).
    - echelon 4y ago
      Seems like something a complete cell count could identify. Different upregulation depending on immune pathway and recognition type.
  - r45c4l 4y ago
    You should watch Dr.House
    - Tabular-Iceberg 4y ago
      You should go to Reddit.
resonious 4y ago
My mother had Lupus. It's kind of another "American medicine failure" story. She'd go to the doctor's office and get berated for being a painkiller junkie even though she never once asked for painkillers. Doctors would just look at her record and assume. When she finally did get a doctor that tried to help, she got put on this weird steroid that made her body a little stronger but at the cost of some brain fog. She was on that drug for 10-odd years before going to a different hospital on a whim. The new doctor concluded that actually the Lupus wasn't even active. It was in remission and had been for years. Turns out, the previous doctor was skipping some routine tests because the results were always the same. Mom got off the drug and her mind got better but her body didn't. Off the drug, she was basically in the same physical state as she was on the drug. Couldn't walk or even sit down for more than a couple hours without pain. So what's going on? She started getting her bones checked to see if there was some kind of alignment problem. There was some old film of her as a toddler that showed her walking funny, and she also once had a bad accident doing sports, which seemed like potential evidence for something skeletal. Before she could figure anything else out, she found a lump and got diagnosed with cancer. It originally looked like regular breast cancer but the breast cancer chemo didn't work. Turns out it's this super-rare "meta-plastic" cancer that nobody at the hospital had ever seen before. She just went through palliative care and hospice then died only a year after finding the tumor. Turns out there were some studies saying the drug she was on for longer than necessary is correlated with rare cancers. Unfortunately I don't have the name of the drug or the details of the cancer on hand right now. Anyway, it's cool to see some research that might eventually help Lupus patients avoid getting yelled at for popping pills (even when not actually popping pills).
- friedman23 4y ago
  Western health care philosophy is just so terrible for these classes of diseases that are just not well understood.
  - aksss 4y ago
    The immune system is not understood well at all, but western medicine does have quantifiable success in treatment of lupus. In the 40’s or 50’s, scientists/clinicians tracked a cohort of representative lupus patients and within two years of diag most were dead. Today lifespan has been greatly extended, protecting the organs being a big advance. IF you have lupus, and IF you get diagnosed, and IF you can afford proper prophylactic drugs and IF you manage your diet, exercise, sleep, stress better that you ever used to, you can usually manage it and hit old age. The western lifestyle is a bigger impediment to health than western medicine.
behnamoh 4y ago
When I see headlines like this, I ask myself: "Is it really necessary to include the nationality of the person if that has nothing to do with the matter at hand?" In this case, a better title would have been "a teen's genome may hold ...".
- nomdep 4y ago
  Extremely important for those doing the research. In order to get funding they must raise awareness and be memorable. They are the ones that uses that teen’s genome, so every press release must mention “the Spanish teen”. It’s branding.
- DoreenMichele 4y ago
  For anything genetic, mentioning ethnicity/nationality is potentially relevant. Some genetic disorders are predominantly found in certain populations. Cystic Fibrosis is predominantly Caucasian. Sickle Cell is predominantly (or perhaps exclusively) African (ancestry). Etc.
valtism 4y ago
I've been quite interested in auto-immune diseases lately. I have a friend with fibromyalgia which latest tests[1] have shown to potentially be an auto-immune disease. The symptoms are similar to lupus, and also similar to what I hear people report as long covid. I don't have a background in medicine, but these all seem related and are all poorly-understood and treated. It is frustrating to watch as those affected have to fight every day just to get the energy to live their lives, constantly changing diets and routines just to try to make sense of what triggers flare-ups in their condition. [1] https://www.jci.org/articles/view/144201 https://www.jci.org/articles/view/144201
- Miner49er 4y ago
  My personal theory is that many long covid cases are people who developed autoimmune diseases either from covid or around the time they got covid.
  - cruano 4y ago
    That's half of the cases on House, M.D. It's not one super rare disease, but a combination of lupus + something else
- mateo- 4y ago
  since you're interested, may i present my childhood illness? https://en.wikipedia.org/wiki/Periodic_fever,_aphthous_stomatitis,_pharyngitis_and_adenitis https://en.wikipedia.org/wiki/Periodic_fever,_aphthous_stoma...
- insaider 4y ago
  I've been struggling with the same sort of thing for 8 years now. I've been to dozens of doctors in several different countries but never got a proper diagnosis. From my own research and observations I'm quite confident it is, as you elude to, an auto-immune related disease. The two major triggers for me are exercise; particularly anaerobic e.g weightlifting, and alcohol. Alcohol actually alleviates the symptoms for a day or more and then undoubtedly i'll struggle for a few days after that. Which points to alcohol's suppressive effects on the immune system. I really really hope this, and similar research[1], turns into something tangible [1] https://med.stanford.edu/news/all-news/2019/04/biomarker-for-chronic-fatigue-syndrome-identified.html https://med.stanford.edu/news/all-news/2019/04/biomarker-for...
chefandy 4y ago
The study linked in this blog post: https://www.nature.com/articles/s41586-022-04642-z https://www.nature.com/articles/s41586-022-04642-z
Zenst 4y ago
I wonder how many people are aware of lupus due to the TV show House?
- karimmaassen 4y ago
  It's never lupus
  - tallguytyo 4y ago
    It's never a good joke.
  - thebeardisred 4y ago
    Thanks to both you and @Zenst for making the joke I came to make. :)
    - Zenst 4y ago
      Appologies, it was not my intent to make a joke, more to acertain how people became aware of the condition Lupus of which myself and it seems, many others awareness was born from that TV show.
tallguytyo 4y ago
Fantastic news, and I'm very glad to see it at the top, but but poor writing IMO. The quote from the ANU researcher about "showing for the first time how ..." links to a 2019 article, and this makes it difficult to distinguish what within the piece is new information and what isn't.
f6v 4y ago
The study mentions CD11c+ B cells aka Ageing B cells (ABCs). These have been detected in other autoimmune conditions and are hypothesized to be pathogenic.
skneko 4y ago
I work in a Spanish university (yes, I'm a filthy academic) and just the other day we were running experiments using a research tool in relation to this new variation of TRL7. This tool is a genomic variation database aggregator that tries to act as an "oracle" of the clinical significance of the variations by running an AI algorithm on the harvested data. Very cool stuff, in spite of my area not being directly related to bioinformatics :)
- aksss 4y ago
  Is this the SIFT and CADD systems referred to in the report: "Bioinformatics analysis revealed a de novo, TLR7 p.Tyr264His (Y264H) missense variant that was predicted to be damaging by SIFT and CADD (Fig. 1a–c (family A) and Supplementary Table 2). This variant was not present in the databases of normal human genome variation (gnomAD, ExAC, dbSNP). Examination of the BAM files together with paternity analysis confirmed that the mutation occurred de novo (Extended Data Fig. 1a, b, d)." I read that and thought that was pretty neat. CADD is Combined Annotation Dependent Depletion, and is "a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses." SIFT stands for Sorting Intolerant From Tolerant, and is "an algorithm that predicts the potential impact of amino acid substitutions on protein function."
- tetris11 4y ago
  I detest these oracles as the variant knowledge base they pull from is often a closed box proprietary product that pulls out variants associated with the disease but rarely find anything actually causative.
mrtri 4y ago
[dead]
rpaddock 4y ago
As my late wife discovered a food sensitivity to Nightshade plants, that are common in our diets, can mimic the symptoms of both Lupus and Rheumatoid Arthritis. When we cleaned up our diets and got chemical based products out of our house, we switched to Hemp based cleaning and body products, her Lupus and RA symptoms went away and never returned. Common Nightshades are: Potatoes Tomatoes Eggplant Peppers (including bell, cayenne pepper, and paprika). Gojo berries are also Nightshades, they are not a 'superfood'. The list is far longer than just those common ones. We are what we absorb from all sources.

209 points by sohkamyung 4y ago

changoplatanero 4y ago
You should elaborate
- AaronNewcomer 4y ago
  - lostcolony 4y ago
- bigDinosaur 4y ago
  There's a not insignificant number of people who think they have lupus who, in reality, most likely do not, to the point where lupus has become something of a meme. It's characteristic of autoimmune disorders to be absolute pains to diagnose correctly as well as they often share symptoms with other disorders and entirely unrelated conditions (e.g. if you keep getting rashes that could be any number of autoimmune disorders or none at all, and more likely to be some environmental allergy than lupus).
  - echelon 4y ago
    Seems like something a complete cell count could identify. Different upregulation depending on immune pathway and recognition type.
- r45c4l 4y ago
  You should watch Dr.House
  - Tabular-Iceberg 4y ago
    You should go to Reddit.

My mother had Lupus. It's kind of another "American medicine failure" story. She'd go to the doctor's office and get berated for being a painkiller junkie even though she never once asked for painkillers. Doctors would just look at her record and assume. When she finally did get a doctor that tried to help, she got put on this weird steroid that made her body a little stronger but at the cost of some brain fog. She was on that drug for 10-odd years before going to a different hospital on a whim. The new doctor concluded that actually the Lupus wasn't even active. It was in remission and had been for years. Turns out, the previous doctor was skipping some routine tests because the results were always the same. Mom got off the drug and her mind got better but her body didn't. Off the drug, she was basically in the same physical state as she was on the drug. Couldn't walk or even sit down for more than a couple hours without pain. So what's going on? She started getting her bones checked to see if there was some kind of alignment problem. There was some old film of her as a toddler that showed her walking funny, and she also once had a bad accident doing sports, which seemed like potential evidence for something skeletal. Before she could figure anything else out, she found a lump and got diagnosed with cancer. It originally looked like regular breast cancer but the breast cancer chemo didn't work. Turns out it's this super-rare "meta-plastic" cancer that nobody at the hospital had ever seen before. She just went through palliative care and hospice then died only a year after finding the tumor. Turns out there were some studies saying the drug she was on for longer than necessary is correlated with rare cancers. Unfortunately I don't have the name of the drug or the details of the cancer on hand right now. Anyway, it's cool to see some research that might eventually help Lupus patients avoid getting yelled at for popping pills (even when not actually popping pills).

friedman23 4y ago
Western health care philosophy is just so terrible for these classes of diseases that are just not well understood.
- aksss 4y ago
  The immune system is not understood well at all, but western medicine does have quantifiable success in treatment of lupus. In the 40’s or 50’s, scientists/clinicians tracked a cohort of representative lupus patients and within two years of diag most were dead. Today lifespan has been greatly extended, protecting the organs being a big advance. IF you have lupus, and IF you get diagnosed, and IF you can afford proper prophylactic drugs and IF you manage your diet, exercise, sleep, stress better that you ever used to, you can usually manage it and hit old age. The western lifestyle is a bigger impediment to health than western medicine.

behnamoh 4y ago

When I see headlines like this, I ask myself: "Is it really necessary to include the nationality of the person if that has nothing to do with the matter at hand?" In this case, a better title would have been "a teen's genome may hold ...".

nomdep 4y ago
Extremely important for those doing the research. In order to get funding they must raise awareness and be memorable. They are the ones that uses that teen’s genome, so every press release must mention “the Spanish teen”. It’s branding.
DoreenMichele 4y ago
For anything genetic, mentioning ethnicity/nationality is potentially relevant. Some genetic disorders are predominantly found in certain populations. Cystic Fibrosis is predominantly Caucasian. Sickle Cell is predominantly (or perhaps exclusively) African (ancestry). Etc.

valtism 4y ago

I've been quite interested in auto-immune diseases lately. I have a friend with fibromyalgia which latest tests[1] have shown to potentially be an auto-immune disease. The symptoms are similar to lupus, and also similar to what I hear people report as long covid. I don't have a background in medicine, but these all seem related and are all poorly-understood and treated. It is frustrating to watch as those affected have to fight every day just to get the energy to live their lives, constantly changing diets and routines just to try to make sense of what triggers flare-ups in their condition. [1] https://www.jci.org/articles/view/144201 https://www.jci.org/articles/view/144201

Miner49er 4y ago
My personal theory is that many long covid cases are people who developed autoimmune diseases either from covid or around the time they got covid.
- cruano 4y ago
  That's half of the cases on House, M.D. It's not one super rare disease, but a combination of lupus + something else
mateo- 4y ago
since you're interested, may i present my childhood illness? https://en.wikipedia.org/wiki/Periodic_fever,_aphthous_stomatitis,_pharyngitis_and_adenitis https://en.wikipedia.org/wiki/Periodic_fever,_aphthous_stoma...
insaider 4y ago
I've been struggling with the same sort of thing for 8 years now. I've been to dozens of doctors in several different countries but never got a proper diagnosis. From my own research and observations I'm quite confident it is, as you elude to, an auto-immune related disease. The two major triggers for me are exercise; particularly anaerobic e.g weightlifting, and alcohol. Alcohol actually alleviates the symptoms for a day or more and then undoubtedly i'll struggle for a few days after that. Which points to alcohol's suppressive effects on the immune system. I really really hope this, and similar research[1], turns into something tangible [1] https://med.stanford.edu/news/all-news/2019/04/biomarker-for-chronic-fatigue-syndrome-identified.html https://med.stanford.edu/news/all-news/2019/04/biomarker-for...

chefandy 4y ago

The study linked in this blog post: https://www.nature.com/articles/s41586-022-04642-z https://www.nature.com/articles/s41586-022-04642-z

Zenst 4y ago

I wonder how many people are aware of lupus due to the TV show House?

karimmaassen 4y ago
It's never lupus
- tallguytyo 4y ago
  It's never a good joke.
- thebeardisred 4y ago
  Thanks to both you and @Zenst for making the joke I came to make. :)
  - Zenst 4y ago
    Appologies, it was not my intent to make a joke, more to acertain how people became aware of the condition Lupus of which myself and it seems, many others awareness was born from that TV show.

tallguytyo 4y ago

Fantastic news, and I'm very glad to see it at the top, but but poor writing IMO. The quote from the ANU researcher about "showing for the first time how ..." links to a 2019 article, and this makes it difficult to distinguish what within the piece is new information and what isn't.

f6v 4y ago

The study mentions CD11c+ B cells aka Ageing B cells (ABCs). These have been detected in other autoimmune conditions and are hypothesized to be pathogenic.

skneko 4y ago

I work in a Spanish university (yes, I'm a filthy academic) and just the other day we were running experiments using a research tool in relation to this new variation of TRL7. This tool is a genomic variation database aggregator that tries to act as an "oracle" of the clinical significance of the variations by running an AI algorithm on the harvested data. Very cool stuff, in spite of my area not being directly related to bioinformatics :)

aksss 4y ago
Is this the SIFT and CADD systems referred to in the report: "Bioinformatics analysis revealed a de novo, TLR7 p.Tyr264His (Y264H) missense variant that was predicted to be damaging by SIFT and CADD (Fig. 1a–c (family A) and Supplementary Table 2). This variant was not present in the databases of normal human genome variation (gnomAD, ExAC, dbSNP). Examination of the BAM files together with paternity analysis confirmed that the mutation occurred de novo (Extended Data Fig. 1a, b, d)." I read that and thought that was pretty neat. CADD is Combined Annotation Dependent Depletion, and is "a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses." SIFT stands for Sorting Intolerant From Tolerant, and is "an algorithm that predicts the potential impact of amino acid substitutions on protein function."
tetris11 4y ago
I detest these oracles as the variant knowledge base they pull from is often a closed box proprietary product that pulls out variants associated with the disease but rarely find anything actually causative.

mrtri 4y ago

[dead]

rpaddock 4y ago

As my late wife discovered a food sensitivity to Nightshade plants, that are common in our diets, can mimic the symptoms of both Lupus and Rheumatoid Arthritis. When we cleaned up our diets and got chemical based products out of our house, we switched to Hemp based cleaning and body products, her Lupus and RA symptoms went away and never returned. Common Nightshades are: Potatoes Tomatoes Eggplant Peppers (including bell, cayenne pepper, and paprika). Gojo berries are also Nightshades, they are not a 'superfood'. The list is far longer than just those common ones. We are what we absorb from all sources.