New Cause Of Autoimmunity Discovered - Age Associated B-Cells

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https://m.medicalxpress.com/news/2017-05-trigger-autoimmune-disease.html



Trigger for autoimmune disease identified
May 11, 2017

Researchers Kira Rubtsova, Philippa Marrack and Anatoly Rubtsov have shown that the transcription factor T-bet inside B cells drives the appearance of Age-associated B Cells (ABCs) and the development of autoimmune disease. Credit: National Jewish Health
Researchers at National Jewish Health have identified a trigger for autoimmune diseases such as lupus, Crohn's disease and multiple sclerosis. The findings, published in the April 2017 issue of Journal of Clinical Investigation, help explain why women suffer autoimmune disease more frequently than men, and suggest a therapeutic target to prevent autoimmune disease in humans.


"Our findings confirm that Age-associated B Cells (ABCs) drive autoimmune disease," said Kira Rubtsova, PhD, an instructor in biomedical science at National Jewish Health. "We demonstrated that the transcription factor T-bet inside B cells causes ABCs to develop. When we deleted T-bet inside B cells, mice prone to develop autoimmune disease remained healthy. We believe the same process occurs in humans with autoimmune disease, more often in elderly women."

Autoimmune diseases occur when the immune system attacks and destroys the organs and tissue of its own host. Dozens of autoimmune diseases afflict millions of people in the United States. Several autoimmune diseases, including lupus, rheumatoid arthritis and multiple sclerosis strike women two to 10 times as often as men. Overall, about 80 percent of autoimmune patients are women. There is no cure for autoimmune disease.

B cells are important players in autoimmune disease. The National Jewish Health research team, led by Chair of Biomedical Science Philippa Marrack, PhD, previously identified a subset of B cells that accumulate in autoimmune patients, autoimmune and elderly female mice. They named the cells Age-associated B cells, or ABCs. Subsequent research showed that the transcription factor T-bet plays a crucial role in the appearance of ABC.

National Jewish Health researcher Kira Rubtsova, PhD, explains why women's stronger immune systems are both a benefit and a curse. Credit: National Jewish Health
Transcription factors bind to DNA inside cells and drive the expression of one or several genes. Researchers believe that T-bet appears inside cells when a combination of receptors on B-cell surfaces—TLR7, Interferon-gamma and the B-cell receptor—are stimulated.

Through breeding and genetic techniques the research team eliminated the ability of autoimmune-prone mice to express T-bet inside their B cells. As a result, ABCs did not appear and the mice remained healthy. Kidney damage appeared in 80 percent of mice with T-bet in the B cells and in only 20 percent of T-bet-deficient mice. Seventy-five percent of mice with T-bet in their B cells died by 12 months, while 90 percent of T-bet-deficient mice survived 12 months.

"Our findings for the first time show that ABCs are not only associated with autoimmune disease, but actually drive it," said Dr. Rubtsova.

ABCs have attracted increasing interests since their discovery in 2011. Dr. Rubtsova and her colleagues at National Jewish Health have expanded their study of ABCs beyond autoimmune disease and are looking at their involvement in sarcoidosis, hypersensitivity pneumonitis and chronic beryllium disease.


The National Jewish Health Chair of Biomedical Research explains explains autoimmune disease. Credit: National Jewish Health
 

Marky90

Science breeds knowledge, opinion breeds ignorance
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What exactly do they do to make mice prone to autoimmunity? Change their gender from male to female? ..

They will probably get grants, but seems there are a lot of questions to be asked directed at the premise for their research.. Ps: I havent read the whole paper.
 

Marky90

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Wish they'd add that to the headline.
I think journals actually should be obliged to demand that. Far to many news stories getting spun like the cure has been found for something, and it`s often mice research (often with alzheimers). That being said, journalists should also be obliged!

Fake news y`all...
 

Hip

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T-bet appears to be the factor in B-cells making mice prone to developing autoimmune disease. The authors said that T-bet appears in the following circumstances:
Researchers believe that T-bet appears inside cells when a combination of receptors on B-cell surfaces—TLR7, Interferon-gamma and the B-cell receptor—are stimulated.
Very interesting that toll-like receptor 7 (TLR7) as well as TLR8 is responsive to single-stranded RNA (ssRNA) from viral infection: TLR7 and TLR8 are the cell's detectors of ssRNA. Ref: 1

This fact might then help explain why ME/CFS is linked to enterovirus, as enterovirus can form chronic B-cell infections which will produce ssRNA in the cell (see: The 3 main viruses linked to ME — enterovirus, EBV & HHV-6 — all infect B-cells).

TLR7 is located intracellularly (located inside the cell), so this receptor will detect the ssRNA being produced inside a B-cell that is chronically infected with enterovirus.

Thus TLR7 activation by viral ssRNA in the cell might be the mechanism by which enterovirus triggers the B-cell autoimmunity that the rituximab research suggests may cause ME/CFS.



If T-bet were a factor behind the triggering of ME/CFS autoimmunity, then reducing T-bet might be a treatment for ME/CFS. T-bet could be reduced by inhibiting interferon-gamma, antagonizing TLR7, and inhibiting the B-cell receptor.

Andrographolide (a herbal extract of Andrographis paniculata) is an interferon-gamma inhibitor, and this study showed it can reduce T-bet. Andrographolide can be bought on AliExpress.

Two compounds, AT791 and E6446 (dihydrochloride), are known to inhibit TLR7. Ref: 1 There is an antihistamine called levocetirizine dihydrochloride (Xyzal) whose molecule contains dihydrochloride, but whether this might work in the same way as dihydrochloride on TLR7 I am not sure (but I found a patent detailing the use of levocetirizine to treat autoimmune disease).

NMDA-receptor antagonists (such as memantine and high-dose transdermal magnesium) have been shown to attenuate B-cell receptor signaling. Ref: 1
 

Hip

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Also available on Amazon from multiple mainstream suppliers.
Yes, if you buy the herb Andrographis paniculata on Amazon or elsewhere, it will contain around 10% andrographolide. If you want 98% pure andrographolide though, the only place I've seen it is on AliExpress. I bought some of that 98% andrographolide a while ago for a different purpose, and at dose of 300 mg daily, it may have had some positive effects on ME/CFS symptoms, but nothing to write home about.
 
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Diwi9

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Yes, if you buy the herb Andrographis paniculata on Amazon or elsewhere, it will contain around 10% andrographolide. If you want 98% pure andrographolide though, the only place I've seen it is on AliExpress. I bought some of that andrographolide a while ago for a different purpose, and at dose of 300 mg daily, it may have had some positive effects on ME/CFS symptoms, but nothing to write home about.
Good information! I get nervous about buying items when I can't read the language. There was a recent case of a woman dying in San Francisco after drinking a Chinese herbal tea mix that was contaminated.

Some of the reviews on Amazon noted that Andrographis paniculata has long been used in Sweden to prevent and/or shorten colds/flus.
 

erin

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There is an antihistamine called levocetirizine dihydrochloride (Xyzal) whose molecule contains dihydrochloride, but whether this might work in the same way as dihydrochloride on TLR7 I am not sure (but I found a patent detailing the use of levocetirizine to treat autoimmune disease).
I went to an internist last Thursday for my flank pain (left side) and GI problems. He examined me and felt that my intestines were very spasmic, rock hard. I thought he was going to do a scan. But he said I need a colonoscopy which I already booked it for next month. I also mentioned all my allergic skin problems, he had prescribed me Xyzal. This is my third day on it, itch is less, but made me more fatigued than my usual ME fatigue. The dr does not know ME and I've not mentioned it. I mentioned all my problems as separate symptoms and he said that he thought they are all related and auto immune - allergic. He also prescribed a medicine for cramping and gas and a probiotic.

I've not used them yet, he said use them when in need. I'm not too bad for gas and bloating at the moment.

Has anyone else use Xyzal? It kind of made me calmer and more normalish. Still, early days.
 

Gondwanaland

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Xyzal. This is my third day on it, itch is less, but made me more fatigued than my usual ME fatigue.
Has anyone else use Xyzal? It kind of made me calmer and more normalish. Still, early days.
How did Xyzal work for you? I tried it 1x in 2016 and 1x yesterday and it multiplied my fatigue x100. Not sure I will take it again tonight.
 

Thinktank

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Levoceterizine (xyzal) is advertised as a non-drowsy antihistamine but that's bs, all antihistamines cause drowsiness in some way or another.
Fexofenadine (allegra) is the mildest antihistamine in terms of causing drowsiness, maybe you could give it a try.