Asthmaasthma phenotypesSally WenzelSARPSevere asthma

I’m phenotyped

th2-dominant

Thanks to the efforts of the SARP researchers and the new era of severe asthma phenotyping, my particular flavor of the disease has finally been described. Drum roll please…………………

It’s called “Long duration Th2 low/mast cell high with remodeling“, asthma.

It probably sounds like a bunch of googly gob, but about half the people with severe asthma have higher than normal amounts of what they call “Th2” cytokines or inflammation. These individuals are labeled Th2-high. The other half of severe asthmatics have lower than usual amounts of Th2 inflammation or what they call Th2 -low If this confuses even more, here’s a brief refresher course on the immune system and asthma:

The main function of our immune systems is to recognize the difference between normal cells (“self”), and invaders (“non-self”). The immune system must then protect “self” and work to eliminate “nonself,” which can include viruses, bacteria, parasites, even cancer cells. The human body has an incredibly intricate system of defense, and uses multiple mechanisms to keep invaders (pathogens) out.

One of these mechanisms is called the adaptive immune system. This system consists of special types of white blood cells called B cells and T cells (often called lymphocytes). B cells make antibodies against foreign invaders so the immune system can “remember” the pathogen and quickly eliminate it in the future. T cells are responsible for either actively killing ( what they call “killer” T cells ), or helping to kill (“helper” T cells) the invading pathogen.
These lymphocytes activate and regulate the immune system by making cytokines, which are chemical signals that tell other cells in the immune system what to do. Of all the types of cells in the body, helper T cells are considered to be the biggest producers of these cytokines. There are two main types of helper T cells: Th1 cells and Th2 cells.

Th1 cells work to eliminate invaders that occur inside our cells (viruses and some intracellular bacteria),while Th2 cells zero in on and destroy pathogens that occur outside our cells (bacteria and parasites). Th1 and Th2 cells each create different cytokines which triggers different effects in the body.

A healthy immune system can “choose” which types of cells to produce and can easily switch back and forth between Th1 and Th2-type responses. An unhealthy immune system can get “stuck” in one of these responses – leading to excessive production of only one type of cytokines.

Most people in the developed world get “stuck” in a Th2 response. This is because our bodies are not exposed to as many parasites and bacteria as in the past (thanks to Lysol, toilets, and water sanitation systems). An immune system without an invader to fight will start attacking anything it can, including pollens, food particles, dust, dander, etc. When Th2 becomes switched on it activates eosinophils and IgE-type reactions which leads to the symptoms we recognize as “allergies”. For some people this can become severe, leading to severe asthma, eczema, and anaphylactic reactions.

For a better understanding on the difference between Th2-high and Th2-low cytokine levels in asthmatics, here’s an excellent article written by my Pulmonologist John Fahy at UCSF.

Per Dr Wenzel, even though I don’t have the typical markers of Th2-high inflammation (ie,high levels of eosinophils, neutrophils, exhaled Nitric Oxide, etc), she believes I do have Th2 inflammation, but probably a different type and in a different location… more than likely in my smaller airways. I also a massive amount of mast cells in my larger airways, which is only seen in people with very severe asthma.

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2 thoughts on “I’m phenotyped

  1. Trust you to be awkward, Stephen. Nothing common, or normal. My consultant said it is better to look for rare variants of common conditions than common variants of rare conditions. So I said “You mean if it is a horse with black and white stripes it is still a horse and not a zebra?” “Yup,” he said. Ask Dr Wenzel if you have a zebra or a horse. (Zebras being rare diseases in the medical world. Probably because they are at the end of the text books and start with Z.)
    Love and gentle hugs
    Kate xxxx

  2. Very cool on the phenotype! I am totally curious where I fit in. Are there new classifications of phenotype from SARP or are these for the SARP 3 peeps?

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