We Might Have Finally Found The Trigger For Autoimmune Diseases

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We Might Have Finally Found The Trigger For Autoimmune Diseases
BY DAVID NIELD
MARCH 08, 2018

“Scientists have identified a chain reaction that explains why our own bodies can turn against healthy cells, potentially transforming the way we look at autoimmune diseases and the way we treat them.”


https://www.sciencealert.com/we-may-hav ... -start/amp

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“The reaction, discovered in 2017 after four years of research in mice, has been described as a "runaway train" where one error leads the body to develop a very efficient way of attacking itself.
The study focussed on B cells gone rogue. Ordinarily these cells produce antibodies and program the immune cells to attack unwanted antigens (or foreign substances), but scientists found an 'override switch' in mouse B cells that distorted this behaviour and caused autoimmune attacks.
"Once your body's tolerance for its own tissues is lost, the chain reaction is like a runaway train," said one of the team, Michael Carroll from Boston Children's Hospital and Harvard Medical School (HMS).
"The immune response against your own body's proteins, or antigens, looks exactly like it's responding to a foreign pathogen."
These B-cells-gone-awry could in turn explain the biological phenomenon known as epitope spreading, where our bodies start to hunt down different antigens that shouldn't be on the immune system's 'kill list'.
Epitope spreading has long been observed in the lab but scientists have been in the dark about how it happens, and why autoimmune diseases evolve over time to target an ever-expanding catalogue of healthy organs and tissues.”

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Abstract
The diversification of the immune response induced by an antigen to new T cell and/or antibody specificities during the course of an autoimmune disease is known as “epitope spreading”. This broadening of the immune response can target epitopes either within the same antigen (intramolecular spreading) or another antigen (intermolecular spreading). Multiple factors are involved in the induction of epitope spreading, including the enhanced display of previously cryptic determinants under the local inflammatory/cytokine milieu, the release of self antigens following tissue damage, the difference in the size and avidity of the epitope-specific T cell subsets and the role of B cells as antigen-presenting cells. Epitope spreading has generally been invoked in the progression and chronicity of the initial (acute) phase of disease. In certain situations, however, epitope spreading has been found to be “protective” or “disease-regulating”. Studies of experimental models have revealed a “window” of therapeutic opportunity in the face of disease-propagating epitope spreading. Understanding the phenomenon of epitope spreading is important for fully defining the pathogenesis of autoimmune diseases and for developing better immunotherapeutic approaches for these disorders.

https://www.sciencedirect.com/science/a ... 2692000039

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In searching the forum by “ epitope“ , I came upon these 2 discussions

viewtopic.php?p=12572#p12572

viewtopic.php?f=58&t=369&p=5939&hilit=epitope#p5939

[D.ap]

The study focussed on B cells gone rogue. Ordinarily these cells produce antibodies and program the immune cells to attack unwanted antigens (or foreign substances), but scientists found an 'override switch' in mouse B cells that distorted this behaviour and caused autoimmune attacks.
"Once your body's tolerance for its own tissues is lost, the chain reaction is like a runaway train," said one of the team, Michael Carroll from Boston Children's Hospital and Harvard Medical School (HMS).

“B cells, also known as B lymphocytes, are a type of white blood cell of the small lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system by secreting antibodies.”

[D.ap]

Abstract

Autoantibodies are frequently observed in healthy individuals. In a minority of these individuals, they lead to manifestation of autoimmune diseases, such as rheumatoid arthritis or Graves’ disease. Overall, more than 2.5% of the population is affected by autoantibody-driven autoimmune disease. Pathways leading to autoantibody-induced pathology greatly differ among different diseases, and autoantibodies directed against the same antigen, depending on the targeted epitope, can have diverse effects. To foster knowledge in autoantibody-induced pathology and to encourage development of urgently needed novel therapeutic strategies, we here categorized autoantibodies according to their effects. According to our algorithm, autoantibodies can be classified into the following categories: (1) mimic receptor stimulation, (2) blocking of neural transmission, (3) induction of altered signaling, triggering uncontrolled (4) microthrombosis, (5) cell lysis, (6) neutrophil activation, and (7) induction of inflammation. These mechanisms in relation to disease, as well as principles of autoantibody generation and detection, are reviewed herein.

Keywords: autoimmunity, autoantibodies, treatment, pathogenesis, mouse models, B cells, diagnosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449453/

[D.ap]

“The reaction, discovered in 2017 after four years of research in mice, has been described as a "runaway train" where one error leads the body to develop a very efficient way of attacking itself.
The study focussed on B cells gone rogue. Ordinarily these cells produce antibodies and program the immune cells to attack unwanted antigens (or foreign substances), but scientists found an 'override switch' in mouse B cells that distorted this behaviour and caused autoimmune attacks.
"Once your body's tolerance for its own tissues is lost, the chain reaction is like a runaway train," said one of the team, Michael Carroll from Boston Children's Hospital and Harvard Medical School (HMS).
"The immune response against your own body's proteins, or antigens, looks exactly like it's responding to a foreign pathogen."
These B-cells-gone-awry could in turn explain the biological phenomenon known as epitope spreading, where our bodies start to hunt down different antigens that shouldn't be on the immune system's 'kill list'.
Epitope spreading has long been observed in the lab but scientists have been in the dark about how it happens, and why autoimmune diseases evolve over time to target an ever-expanding catalogue of healthy organs and tissues.”

“Epitope Spreading: Definition

That means, in essence, that a primary autoimmune or inflammatory process may cause tissue damage in such a manner that certain protein components that are immunologically “hidden” from the immune system become “revealed” and evoke a secondary autoimmune response.”