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Author Topic: Elite Controller-related NEWS UPDATE  (Read 2338 times)

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Offline emeraldize

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  • Posts: 3,347
Elite Controller-related NEWS UPDATE
« on: November 06, 2010, 08:10:34 AM »

http://www.sciencenews.org/view/generic/id/65088/title/Immune_gene_variants_help_stop_HIV


Immune gene variants help stop HIV
Research on ‘elite controllers’ might lead to better drugs or vaccine
By Nathan Seppa
Web edition : Thursday, November 4th, 2010


Variations in an immune-system gene account for at least part of the uncanny ability of some people to withstand an HIV infection without developing AIDS, researchers report online November 4 in Science. The study confirms past data linking the gene, called HLA-B, to HIV defense and narrows researchers’ focus to molecular changes brought on by particular variations in the gene.

About one in 300 people with HIV are “elite controllers.” Though infected with the virus, their immune systems control the disease such that it rarely progresses, even without medicine. Scientists have long thought that finding the genetic peculiarities underlying this protection could help to create drugs or a vaccine against HIV. Recently, scientists found that elite controllers make excess amounts of a protein called p21, which might contribute to protection (SN: 11/20/10, p. 9).

Previous research had hinted that HLA gene variations played a role in elite controllers by influencing a patient’s HIV viral load and disease progression. HLA genes encode immune proteins called human leukocyte antigens, which are central to immune function.

In the new study, a multinational consortium of researchers identified more than 1 million genetic variations in blood samples from people with HIV, some elite controllers and some not. The scientists were able to spot more than 300 variations that differed substantially between the groups, says study coauthor Paul de Bakker, a geneticist at Harvard Medical School and Brigham and Women’s Hospital in Boston.

For example, a variant called HLA-B*57:01 showed up five times as often in controllers as in the others. Several variants of other genes appeared two to four times as often in controllers as well, but alternate forms of the HLA-B gene stood out in the analysis.

The HLA-B protein comes in many varieties, each encoded by a slightly different blueprint — a variation — of the HLA-B gene. The protein provides an essential immune function, collecting viral fragments in cells and displaying them on the cell surface for inspection by marauding immune enforcers called CD8 T cells, which give each protein a thumbs up or thumbs down. If the CD8 T cell disapproves of a protein fragment, the whole cell gets destroyed. While it may seem drastic to tag a cell for disposal, the extreme measures stop a virus before it can commandeer the cell to mass-produce more virus, says study coauthor Bruce Walker, an immunologist at Harvard Medical School and Massachusetts General Hospital in Boston.

“I think this is a really good paper. It’s very interesting,” says Alasdair Leslie, an immunologist at University of Oxford in England, whose group did earlier work linking CD8 T cell function to HLA proteins. “This strengthens the argument that HLA [variations] and presumably CD8 T cell responses are important,” he says. “It does give hope to the idea that harnessing this response in a vaccine could work.”

By analyzing the structure of the HLA-B gene variants and noting which were linked to protection against HIV, the researchers were able to zero in on a handful of amino acids — the molecular building blocks of proteins — that are instrumental in the all-important binding of HLA-B proteins to HIV fragments in a cell.

“This is a really exciting step toward a kind of pie-in-the-sky goal,” says statistical geneticist Alison Motsinger-Reif of North Carolina State University in Raleigh. Elite controllers represent a medical mystery, she says. “If we can understand what’s different about their biology, it will open up new targets [for HIV] drugs or vaccines.”

This molecular precision represents new terrain for scientists seeking to explain how controllers stay healthy, because it reveals what these amino acids are and even where they sit on an HLA-B protein, de Bakker says.

But that still doesn’t explain how they work.

“We’ve been looking for needles in a haystack,” Walker says. “Now we need to interrogate the needles.”


Offline ElZorro

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Re: Elite Controller-related NEWS UPDATE
« Reply #1 on: November 06, 2010, 10:20:11 AM »
great stuff...thanks for the post, Em

Offline OzPaul

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  • Posts: 410
  • a very blessed 29 year ltnp
Re: Elite Controller-related NEWS UPDATE
« Reply #2 on: November 06, 2010, 10:24:39 PM »
Hey Em

Thanks for the interesting post !  I am told I don't have the HLA B57, however I do have a 'bad' one  HLA B35.  I continue participation in the International HIV Controllers study in Boston as well as the ltnp study at the NIH in Bethesda Maryland and an ltnp study in Sydney, Australia.  There are several other forum members like you and me who participate in these and other studies.

all the best,
Paul

Offline emeraldize

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Re: Elite Controller-related NEWS UPDATE
« Reply #3 on: November 06, 2010, 10:55:16 PM »
Hi OzPaul,

I was participating and planned to continue at MGH, even though I'm now on meds, but they would not reimburse my mileage to and from the airport, my parking and another very reasonable expense. So, I'm no longer participating. Last year, they covered mileage and I believe, parking, too (not motivated enough to doublecheck the paperwork on it). I and others are a lot closer than California and Australia and it is not reasonable to ask a study participant to cover such costs. We're talking roughly $75 wprth of expenses I had to eat. So, I'm done with the study.

Offline OzPaul

  • Member
  • Posts: 410
  • a very blessed 29 year ltnp
Re: Elite Controller-related NEWS UPDATE
« Reply #4 on: November 07, 2010, 12:40:00 AM »
Hi Em

That's a shame you're not still in the study. I think they're looking at decentralizing the study a bit to more places around the country. I was there a short while ago and did not have any problems. Sometimes with bureaucracies, things get a bit problematic. Sorry you've dropped out. When did you go on medications ?  Are you still in the NIH study ?

Cheers and good wishes

Paul  xo

Offline emeraldize

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  • Posts: 3,347
Re: Elite Controller-related NEWS UPDATE
« Reply #5 on: November 07, 2010, 08:28:59 AM »
Hi Oz,

I feel similarly. In fact, I was told one of the MGH researchers was keen on following me specifically as I moved into being medicated having started with them treatment-naive. To answer your question, I started in early October. As regards the NIH study, they've called several times and I simply need to let them know I've begun and learn if they wish, for any reason, to follow me now that I'm on meds. It's possible. One never knows what a researcher might wish to glean given an opportunity to witness change in a subject.

I am hopeful, with the intensity and variety of research going on worldwide, that something powerful and good for all of us is going to occur. I truly think, meditatively, of HIV being wiped out and everyone being able to look each other in the eye and say, " Well, let's handle the next one a llittle differently, shall we?" Because there will be another one, some time and the world had better learn how devastating stigma, access to meds, biased education programs and complete fear combined to worsen this siege.

I understand scientifically this may never occur, but in terms of how I think and envision, it is THE only vision I choose to have as status quo is not delivering quality of life or even life itself for many worldwide. And, when I think/meditate, I think of the many people who, on top of having HIV, cannot eat properly, cannot access meds, cannot possibly survive without change in this world.

BTW, Oz, regarding expense reimbursement, I don't believe this is about bureaucracies malfunctioning, I think it was a matter of someone didn't think about such details when writing the protocol for this revised study. So unless and until they straighten it out, I'm off study. I've wondered if the curious researcher knew it was $75, if she would offer to pay and instigate a protocol amendment. I won't pay such expenses again--it's better to buy food with such money or donate it to a cause.                                  
« Last Edit: November 07, 2010, 07:03:42 PM by emeraldize »

Offline natthai

  • Member
  • Posts: 130
  • The truth is not determined by majority vote.
Re: Elite Controller-related NEWS UPDATE
« Reply #6 on: November 09, 2010, 02:56:14 PM »
Hey Em

Thanks for the interesting post !  I am told I don't have the HLA B57, however I do have a 'bad' one  HLA B35.  I continue participation in the International HIV Controllers study in Boston as well as the ltnp study at the NIH in Bethesda Maryland and an ltnp study in Sydney, Australia.  There are several other forum members like you and me who participate in these and other studies.

all the best,
Paul

Hey Paul and other Elite controllers, could you post a reply with a summary of your lab results. I would be interested to know how the disease progressed, at what point you learned you were a non progressor or controller etc and what the numbers looked like.
Infection date: February 14, 2010 (yeah really)
08/03/2010 - CD4 621 (27%) VL 72,250
25/03/2010 - CD4 981 (28%) VL 122,719 <-started anti-oxidants (ABCDE, Se, ALA, NAC)
11/08/2010 - CD4 1,365 (31%) VL 5,451

 


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