Why did I get Sarcoidosis? Why me?
This is a simplified overview of the full paper "The Angiotensin Hypothesis - how sunlight fuels the run-away inflammation of
Always refer to the full paper to resolve any points of confusion
It is normal for your body to generate an immune response when challenged by foreign matter such as Microbes and Allergens. The immune system has a special type of cell that it forms when the Lymphocytes (White Blood Cells) detect a threat. They are called Macrophages, and their purpose is to secrete caustic chemicals (called Chemokines and Cytokines) that allow the macrophages in the inflammed tissue to digest the invader and the resulting dead tissue
Sarcoidosis is a run-away immune inflammatory response. It is not caused by a hyper-sensitivity, it is caused by a normal response to an invader that just gets out of control, producing run-away inflammation far in excess of what is needed to overcome the threat.
In Sarcoidosis the macrophages form into colonies called Granuloma, where the high concentrations of a hormone called 1,25-dihydroxyvitamin-D3 help the macrophages grow into even more potent Epithelioid Giant Cells. Here is a view of a granuloma through a low power microscope. The tissue has been stained with a chemical dye so that the lymphocytes (WBC) appear black to the microscope.
You can see a ring of lymphocytes defining the periphery of the granuloma (yellow arrows) with the 'insides' consisting of a few lymphocytes, immature macrophages (called monocytes), macrophages and epithelioid giant cells (white arrow). What you can't see are the biochemicals. The most important of these is the secosteroid hormone 1,25-dihydroxyvitamin-D3, Angiotensin II, NuclearFactor-kappaB (in the cells), and the major Cytokines: Interferon-Gamma, TNF-alpha, and the numerous Interleukins.
|Click on image for detailed view|
Sarcoid Granuloma (10X)
This is a granuloma located adjacent to a bronchiole.
The surface of the tissue is covered by respiratory epithelium.
The yellow arrows point to the external circle of lymphocytes.
The white arrow points to a multinucleated giant cell admixed several mononuclear macrophages.
There is no central necrosis (non-caseating) (all cells are healthy)
(Description By:Melinda Sanders, M.D. ) (Image Contrib. by: UCHC )
For a detailed insight into Granuloma, Click here for Dr Yale Rosen's site
Sadly, a certain class of microbes has learnt how to live in the very harsh environment of the granuloma. They can live and multiply in the very environment that is meant to kill and digest them. The body can still sense they are there, and the concentrations of the inflammatory chemicals increase to a point where the inflammation starts to become widespread. This leads to the hyper-inflammation of Sarcodiosis.
Here is an electron microscope photograph of the organism "Rickettsia" living in the granuloma of a sarcoid patient. The magnification is 84 000 times, so the image is over a million times larger than Doctors can see through their optical microscopes. Not only are the organisms healthy, they are replicating by dividing into two, just like a human embryo. These Rickettsia microbes are spread by ticks. This patient caught their Sarcoid from a tick bite, not from anything they inhaled.
|Click on image for detailed view|
Nilsson K, Pahlson C, Lukinius A, Eriksson L, Nilsson L, Lindquist O: "Presence of Rickettsia helvetica in granulomatous tissue from patients with sarcoidosis". J Infect Dis 2002 Apr 15;185(8):1128-38 [Medline]
So why did this happen to me? Lots of people get attacked by microbes and it never turns into Sarcoidosis. So why me?
Every body can create granuloma when it is necessary. For example, when fighting tuberculosis, granuloma are formed, but they normally break down and die (necrosis,caseation) after they have done their job of killing and digesting the TB bacteria.
In Sarcoidosis these granuloma do not die, they remain healthy (non-necrotic, non-caseating). Why?
Well, it all starts with the stem cells. Your blood stem cells. The hormone 1,25-dihydroxyvitamin-D3 (1,25-D) makes the stem cells form into monocytes, the simplest element of the granuloma. Everybody's stem cells do this. As the monocytes grow and mature into Macrophages, also under the influence of 1,25-D, the concentration of 1,25-D in the tissues grows very high. At this point 1,25-D becomes a Paracrine mediator, it acts on the local tissues and cells. Some of it gets into the bloodstream, and circulates around the body performing the normal functions of a hormone. But in the inflamed tissue it grows very high in concentration, very high indeed.
A sarcoid patient's body is lacking some genes that limit the maximum concentration of 1,25-D. It builds up and becomes so concentrated in the inflamed tissues that some of the macrophages even grow into (differentiate into) huge Epithelioid Giant Cells.
Nobody knows exactly what genes those are. There are several research groups working on trying to identify them.
You still haven't told me why I got Sarcoid granuloma and others didn't
Let's try it from the other direction.
When you were born you inherited a "genetic pre-disposition" to develop Sarcoid granuloma. Specifically, your body is unable to regulate the concentrations of the hormone 1,25-dihydroxyvitamin-D.
The body manufactures this hormone from sunlight. But it is also manufactured in Granuloma.
You might have noticed, as a child, maybe you were sometimes sick after a day of sunbathing at the beach. Maybe you vomited when you got home, or maybe you just felt off-color for a few days after the sunbathing. Then again, maybe the sensitivity was there but you just learned to live with it. You just assumed that sun-bathing always felt like that, that it was 'normal'...
Maybe you never noticed anything at all until you started getting the symptoms from the sarcoid inflammation. The fatigue. The lack of energy. That feeling of continual weakness (Asthenia). The profuse sweating. These symptoms are what you get when the level of 1,25-D in your blood gets too high. These are the symptoms of 'Hypervitimanosis D'. These come from the run-away production of 1,25-D in the sarcoid granuloma.
You needed two elements to progress into the full-blown inflammation of Sarcoidosis. You already had the genetic pre-disposition, but you still needed a serious challenge to your immune system. An infection.
When your body was attacked by the microbes, your immune system dutifully started making Macrophages to try and digest the foreign bacteria. But, because your body cannot properly regulate the 1,25-D it manufactures, the process started to get way out of hand. The 1,25-D levels in the inflamed tissue kept rising. Macrophages started to change into Giant Cells. And the non-caseating granuloma of Sarcoidosis started to form.
To add insult to injury, the microbe that was attacking you was of a species that was able to live in the granuloma, and instead of digesting the bacteria, granuloma actually helped to shield the bugs from the antibiotics your Doc was using.
Chances are that it took years of suffering before your Sarcodiosis was diagnosed. During all this time the bacteria were slowly spreading throughout your body. Maybe Doc prescribed Prednisone to try and reduce the inflammation, and thus made it even easier for the infection to spread.
Every Sarcoidosis patient's situation is a little bit different. Different microbes. Different organs attacked. Different degrees of dysfunction. But it is all the same disease. The same simple disease. With the same simple cause.
(C) Copyright 2002, SarcInfo.com, All Rights Reserved
Sarcoidosis Information Discussion Info Message Board Forum