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Autoinflammatory Diseases

Body invaders: How the body protects us

A healthy immune system: Your body’s defence against germs

We all know that a healthy immune system is essential to fight off invading germs that can cause illnesses or disease. These include common viruses (causing colds or the flu) that seem to plague us every winter, or bacteria (such as streptococcus which can cause a bad sore throat).

The skin and mucosa (e.g. inner lining of the nose) act as frontline barriers to prevent germs from entering the body. They are coupled with our saliva, sweat, and tears (which are the body’s ‘chemical’ defences), which contain substances (such as enzymes) that can kill germs. 

If germs manage to enter the body, the immune system forms the next line of defence to prevent them from growing and multiplying. The immune defence system consists of patrolling cells and messenger substances (cytokines) that circulate in the blood, which detect and fight invading germs.

Infection: When germs invade

Find out how some immune system defences become active in patients with autoinflammatory diseases, even when the body has not been exposed to invaders, causing “friendly fire” and inflammation inside the body.

When germs invade the body causing an infection, two parts of the immune system work together to fight the invaders:

  1. A typical infection is first fought by the built-in response to invaders (innate immune system) through the process of inflammation, which attracts cells to “eat” the invaders (think: Pac-man™!). If this is not sufficient to destroy them, the acquired immune system assists.

  2. The acquired immune system “learns” about the germ and then develops antibodies specifically targeted to that germ. The antibodies bind to and clump the germs together so they can be destroyed. The acquired system also “remembers” the germ and can produce the germ-specific antibodies very rapidly from the “immune memory” if the same germ invades the body again. We take advantage of the body’s ability to remember previous invasions by germs when we get vaccinated against diseases.

http://www.periodicfevers.com/globalassets/periodicfevers22/graphs/threshold-value.png

Development of a healthy immune response to germs

 

Friendly fire: Autoinflammatory diseases

What are autoinflammatory diseases?

Autoinflammatory diseases are conditions where the inflammatory response appears to occur automatically or “on its own”, instead of in response to invading germs. This autoinflammation involves the nonspecific innate immune system[1] and occurs periodically in some people or continuously (chronically) in others. 

During an autoinflammatory response, the innate immune system is activated even though no germs are present in the body. (This means that the immune cells act as if they were fighting germs, resulting in an inflammatory response that affects the entire body.[1]) This causes a disease flare with typical symptoms including fever, rash, joint swelling, pain, and fatigue.[1]

Why does this happen? 

There are various causes of autoinflammatory diseases:[1]

Genetic mutations

  • Hereditary

  • Caused by changes in the “instructions” (DNA) for the innate immune system

  • Includes periodic fever syndromes (CAPS, FMF, TRAPS, and HIDS/MKD)

Trigger factors

  • Substances created during chemical reactions in the body (metabolic products) or foreign substances

  • Cold or cooling air, or temperature changes (CAPS), stressors (all periodic fever syndromes), or even vaccinations (HIDS/MKD)

Multiple/unknown causes

  • Can cause a patient to develop: Systemic juvenile idiopathic arthritis, or and several commonly occurring diseases, such as gout, pseudogout, type II diabetes, and atherosclerosis 

CAPS: Cryopyrin-associated periodic syndromes, FMF: Familial mediterranean fever, TRAPS: Tumour necrosis factor receptor associated periodic syndrome, HIDS/MKD: Hyperimmunoglobulinemia D syndrome/Mevalonate kinase deficiency

The culprit: IL-1β

Interleukin-1 beta (IL-1β) is a messenger of the nonspecific innate immune system that can play a special role in many autoinflammatory diseases, including the promotion of the inflammatory response.[2] What do we mean by messenger? These are signals that communicate to the immune cells to come to the site where invaders are.

http://www.periodicfevers.com/globalassets/periodicfevers22/graphs/wirkungen_il-1beta.png

Effects of IL-1β (modified according to [2])

IL-1β has different effects on various parts of the body:[2-6]

http://www.periodicfevers.com/globalassets/periodicfevers22/graphs/graph1.png

 

 

References:

  1. Ciccarelli F, De Martinis M, Ginaldi L. Curr Med Chem 2014; 21: 261–269.
  2. Dinarello CA: JEM 2005; 201: 1355–1359.
  3. Dall, L, Standford JF. Available from: http://www.ncbi.nlm.nih.gov/books/NBK324.
  4. Ceciliani F, Giordano A, Spagnolo V. Protein Pept Lett 2002; 9: 211–223.
  5. Nouri AME, Panayi GS, Goodman SM. Clin Exp Immunol 1984; 55: 295–302.
  6. Rare Diseases UK. About Rare Diseases. Available from: https://www.raredisease.org.uk/what-is-a-rare-disease/
A minute change in DNA can have big impact

Here’s our current understanding of the science behind the tiny DNA change(s) that lead to rare periodic fevers.

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Periodic Fevers

December 2015 - GLDEIM/ACZ885/0044