What Does Auto Inflammatory Mean

They are a group of illnesses which are manifest by Fever and inflammation affection of Joints-Arthritis, Skin-Dermatitis or Rashes, Eyes iritis and bones Osteomyelitis. They all have in common excessive activation of components of the immune system. The immune system has two components or arms called Innate and Adaptive. The innate arm functions through phagocytic cells, which eat up(phagocytose) bacteria and foreign material. They are found in the circulation and named Polys because their nucleus has a shape which differs from the single nucleus of the mononuclear monocytes, which are also called macrophages. Phagocytic cells also are in the liver, spleen,lungs, brain and all tissues including the lining of the blood vessels. When these cells see

Danger and are activated, they produce a series of messenger molecules which signal other cells for help. These are called Inter-Leukins or molecules going between the hoer white cells. They are thus inflammatory both locally and systemically(inflammation).

The adaptive immune arm is made up of a Mononuclear T cells and B cells which amplify and localize the invader in a very specific manner by Delayedhypersensitivity(T Cells) or by Antibodies(IgG,A,M,D and E) produced by B cells and plasma cells which function to localize the specific danger to the site of the penetration of the bodies integrity(skin mucous membranes get etc).The

localization which follows, results in inflammation. The interleukins(ILs) accomplish this and are named usually by a number IL-1,IL-6,IL-12IL-18 etc, but also as named ILs such as TNFa, or Tumor Necrosis Alpha. The latter which has been proven to be the most important cause of inflammation in Rheumatoid arthritis(RA), has caused scientists to manufacture antibodies against

IL-s block their function. These have been proven very successful in treating RA and other forms of inflammatory arthritis, and so caused a revolution in our understanding of autoimmune diseases and their treatment. It is likely that understanding the mechanisms of the AutoInflammatory diseases i.e. their individual interleukin profile and the individual triggers which provoke

them will provide both the understanding and perhaps new treatments to control or cure them.

At this time AutoInflammatory Diseases number 11 with their variations on each one confusing the issue.

1. Familial Mediterranean Ferver (Familial Hebbernian Fever)

2. TNF Receptor Associated Periodic Syndrome (TRAPS)
3. Hyper IgD Syndrome
4. Muckle Wells Syndrome
5. Familial Cold AutoInflammatory Syndrome
6. Neonatal onset inflammatory disease(NOMID)
7. Chronic infantile neurologic cutaneous and articular syndrome(CINCA)
8. Pyogenic sterile arthritis,pyodrmagangreosum,acne(PAPA) syndrome
9. Blau Syndrome
10. Chronic recurrent multiocal osteomyelitis and congential dyserythropoietic anemia(Majeed syndrome)
-Oliver J. Lawless, MD FACR

What:

The science of autoinflammatory diseases has progressed rapidly since the term was first coined in the late 1990s in an effort to distinguish this distinct group of illnesses from the more well-defined autoimmune diseases, such as rheumatoid arthritis and lupus. Advances in genetic technologies have expanded the understanding of the molecular and cellular basis of autoinflammatory diseases and have broadened the field to include disorders that no longer fit within the original classification. This classification was first established with the discovery of the gene mutation responsible for an undefined familial disease characterized by prolonged fevers and severe localized inflammation. The gene coded for the tumor necrosis factor (TNF) receptor and the disorder is now known as the TNF receptor-associated periodic syndrome, or TRAPS. In line with other similar diseases, autoinflammatory disorders were defined by episodes of seemingly unprovoked inflammation without high-titer autoantibodies or antigen-specific T lymphocytes. Both are indicators of autoimmune diseases, which involve the adaptive immune system. The authors of the paper appearing in the current issue of Cell, however, argue that the definition needs to be updated. In an effort to converge the clinical concept of autoinflammatory diseases with advances in the basic science of immunity, they suggest a revised classification that focuses on abnormally increased inflammation mediated predominately by the innate immune system, with a significant host predisposition. The host predisposition could result from genetic factors or could be triggered by gene-environment interactions.

Reference:

Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory Disease Reloaded: A Clinical Perspective. Cell; 2010 March 19;140:784-790.

Auto inflammatory is relatively a new category of immune diseases that are proving to differ from auto-immune diseases. However, auto immune and auto inflammatory diseases, do share common traits. They both are a result of the immune system attacking the body’s own tissues and they both trigger increased inflammation.

Auto inflammatory diseases arise from disorders with the innate immune system. We have the adaptive immune system which selectively targets and fights infectious agents using antibodies. Then we have the innate immune system which fights anything in the body that it recognizes as foreign or non-self with a general and immediate response. Autoimmune and inflammatory both involve the adaptive immune system. The hallmark for innate immunity is inflammation.

When the innate and adaptive immune systems are working together correctly they present an effective defense against disease. However, sometimes the body attacks its own tissues by mistake. For disorders of the adaptive immune system this is referred to as autoimmunity. For disorders of the innate immune system the term auto inflammatory has become the gold standard.

Auto inflammatory disorders are characterized by intense episodes of inflammation that result in such symptoms as fever, rash, or joint swelling.

To better explain this process of our immune system picture your body attacked by a virus or a foreign agent. When your body defends you against these intruders it’s because it notices these viruses and or germs and kills them. When this system of defense doesn’t work it causes your body harm. Immune cells can mistake your own cells as invaders and attack them. This results in your body attacking both good and bad cells. When this process happens and affects many parts of your body this is called auto immunity (meaning self immunity).

Significant conceptual breakthroughs in our understanding of the molecular basis of inflammatory mechanisms in general have occurred in the past fourteen years with successive identification of genetic basis of all the known hereditary periodic fever and their association with the innate immune response. (Lippincott Williams& Wilkins)

To better understand the differences between auto immune and inflammatory diseases scientist’s and Dr’s have found genetic testing to help differentiate them. They discovered this by finding a gene mutation responsible for an undefined familial disease, and gene coded for the tumor necrosis factor (TNF) receptor known as TNF receptor associated periodic syndrome or TRAPS. This was discovered by Dr. Kastner and his group at NIH.

Why it’s so important to be properly diagnosed when having an auto inflammatory disease is because of the strong predisposition to type AA amyloidosis-the most common yet potentially fatal complication of auto inflammatory disease. Amyloids are harmful proteins that build up in vital organs resulting in failure.