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Scientists discover how to 'switch off' autoimmune diseases

melihtas

Senior Member
Messages
137
Location
Istanbul Turkey
Link to full text of the study: Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy

Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy

Abstract

Antigen-specific immunotherapy combats autoimmunity or allergy by reinstating immunological tolerance to target antigens without compromising immune function. Optimization of dosing strategy is critical for effective modulation of pathogenic CD4+ T-cell activity. Here we report that dose escalation is imperative for safe, subcutaneous delivery of the high self-antigen doses required for effective tolerance induction and elicits anergic, interleukin (IL)-10-secreting regulatory CD4+ T cells. Analysis of the CD4+ T-cell transcriptome, at consecutive stages of escalating dose immunotherapy, reveals progressive suppression of transcripts positively regulating inflammatory effector function and repression of cell cycle pathways. We identify transcription factors, c-Maf and NFIL3, and negative co-stimulatory molecules, LAG-3, TIGIT, PD-1 and TIM-3, which characterize this regulatory CD4+ T-cell population and whose expression correlates with the immunoregulatory cytokine IL-10. These results provide a rationale for dose escalation in T-cell-directed immunotherapy and reveal novel immunological and transcriptional signatures as surrogate markers of successful immunotherapy.


Link to MedicalXpress Article about the study: Scientists discover how to 'switch off' autoimmune diseases

Scientists discover how to 'switch off' autoimmune diseases

Scientists have made an important breakthrough in the fight against debilitating autoimmune diseases such as multiple sclerosis by revealing how to stop cells attacking healthy body tissue.

Rather than the body's immune system destroying its own tissue by mistake, researchers at the University of Bristol have discovered how cells convert from being aggressive to actually protecting against disease.

The study, funded by the Wellcome Trust, is published today [03 September] in Nature Communications.

It's hoped this latest insight will lead to the widespread use of antigen-specific immunotherapy as a treatment for many autoimmune disorders, including multiple sclerosis (MS), type 1 diabetes, Graves' disease and systemic lupus erythematosus (SLE).

MS alone affects around 100,000 people in the UK and 2.5 million people worldwide.
Scientists were able to selectively target the cells that cause autoimmune disease by dampening down their aggression against the body's own tissues while converting them into cells capable of protecting against disease.

This type of conversion has been previously applied to allergies, known as 'allergic desensitisation', but its application to autoimmune diseases has only been appreciated recently.

The Bristol group has now revealed how the administration of fragments of the proteins that are normally the target for attack leads to correction of the autoimmune response.
Most importantly, their work reveals that effective treatment is achieved by gradually increasing the dose of antigenic fragment injected.

In order to figure out how this type of immunotherapy works, the scientists delved inside the immune cells themselves to see which genes and proteins were turned on or off by the treatment.
They found changes in gene expression that help explain how effective treatment leads to conversion of aggressor into protector cells. The outcome is to reinstate self-tolerance whereby an individual's immune system ignores its own tissues while remaining fully armed to protect against infection.

By specifically targeting the cells at fault, this immunotherapeutic approach avoids the need for the immune suppressive drugs associated with unacceptable side effects such as infections, development of tumours and disruption of natural regulatory mechanisms.

Professor David Wraith, who led the research, said: "Insight into the molecular basis of antigen-specific immunotherapy opens up exciting new opportunities to enhance the selectivity of the approach while providing valuable markers with which to measure effective treatment. These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat."

This treatment approach, which could improve the lives of millions of people worldwide, is currently undergoing clinical development through biotechnology company Apitope, a spin-out from the University of Bristol.
 

RL_sparky

Senior Member
Messages
379
Location
California
http://www.telegraph.co.uk/health/h...switched-off-by-retraining-immune-system.html


“In allergies the immune system mounts a response to something like pollen or nuts because it wrongly believes they will harm the body.

“But in autoimmune diseases the immune systems sees little protein fragments in your own tissue as foreign invaders and starts attacking them.

“What we have found is that by synthesising those proteins in a soluble form we can desensitise the immune system by giving an escalating dose.”

The team hope that the breakthrough could lead to the development of immunotherapies for individual conditions, based on the protein or antigen that the body is responding too.
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
JE has previously commented that these "induced" autoimmune conditions in animal models are not necessarily useful for comparison with natural autoimmune disorders in Humans, so I'm guessing he will consider it mostly speculation at this point.

This is an interesting idea, but I personally have many reservations about whether it could be useful in a natural autoimmune illness - it first needs to be demonstrated in a real autoimmune illness - merely measuring T-Cell responses is interesting, but not proof that the illness has been suppressed. Besides that, it probably requires very tight control and monitoring of dosages due to the kinetics involved for it to be safe in Humans. Which in turn needs radical new drug delivery methods.
 
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