Surprise: Th2 cells, inflammation high in both allergic, non-allergic eczema

When I talked to Jon Hanifin last year he mentioned an intriguing fact: eczema comes in two general types. About 80% of atopic eczema patients have allergies and high levels of IgE antibodies. But twenty per cent of patients have eczema without allergies.

The technical term for allergic eczema is “extrinsic” atopic dermatitis; the non-allergic kind is “intrinsic” AD.

Production of IgE—and most antibodies—is activated by type 2 helper T cells. So scientists have generally assumed that extrinsic AD patients had overactive type 2 helper T cells. But new research shows that type 2 helper T cells are overactive in both intrinsic and extrinsic AD patients.

The scientists, led by Emma Guttman-Yassky at Rockefeller University in New York City, analyzed skin and blood samples from 42 extrinsic and 9 intrinsic AD patients, looking at molecular and cellular differences in the immune system and the skin.

They found that type 2 helper T cell activation is actually higher in intrinsic AD patients than extrinsic AD patients. In fact, markers of inflammation in general are higher in intrinsic AD.

Figure 6 from the paper. Scientists now resort to "word clouds" to convey the complexity of molecular biology!

The results are surprising. Patients with intrinsic AD generally do not go on to develop asthma or allergic rhinitis; yet if you just looked at their helper T cells you’d think they were guaranteed to experience even more severe allergies than those suffered by extrinsic AD patients.

So what's keeping down the IgE levels in intrinsic AD? In the paper, the authors speculate freely, but so far there is no answer.

It also appears that a special class of helper T cells known as type 17 (so-called because they produce the signaling molecule IL-17A) are also more active in intrinsic than extrinsic AD. It’s not clear yet how scientists might  use this knowledge to design therapies more specific than current T cell-suppressing options such as ciclosporin, which can have severe side effects.

The research suggests that future T-cell related therapies will likely be similar for intrinsic and extrinsic AD, despite the different nature of the disease in the two patient groups.

Hat tip to KMO.

Antibodies, parasitic worms, and cures

Funny vignette: home from work today--I have to bike up a steep hill to get home, and then I'm always hot and sweaty, which triggers the itch. I'm sitting on the floor leaning against the couch scratching the backs of my knees. Voov toddles over and helps me scratch. Shmoop joins in too-- all three of us scratching away at my legs.

Thanks, kids. Though scratching is a department I usually don't need much help with.

I've been reading up on the genetics of eczema. When I've managed to get my head around the subject I'll try to write about it. Suffice it to say that filaggrin is only part of the whole picture, which is complex enough that this picture doesn't do it justice.

In the academic literature, eczema is referred to as "atopic dermatitis" (AD). I always thought this was disingenuous on the part of doctors, to use fancy words that mean the same thing as plain words, in order to maintain the illusion of expertise. "Dermatitis" obviously means "skin inflammation," and I assumed "atopic" meant "we don't know what the hell causes it." (Now I know that would be "idiopathic.") A Google definition search reveals that "atopy" actually has a specific meaning: "allergic hypersensitivity affecting parts of the body not directly in contact with the allergen." Who knew?

Anyway-- eczema, or AD, covers a whole spectrum of disorders. I would like to be as clear on this blog as possible about what I mean by eczema and how it might be cured. You might be interested to know, for example, that two major types of eczema have been identified: "extrinsic" and "intrinsic." Extrinsic AD affects 70-80% of adult patients and involves high levels of circulating IgE antibodies and reactions to environmental allergens. The remainder of adult patients have intrinsic AD, which is defined as the kind that DOESN'T involve high IgE levels or allergies.

IgE is one of five antibody types. IgE is the kind involved in allergies-- when mast cells and basophils bind IgE, they release histamine, which triggers inflammation. IgE is also, somehow, protective against parasitic worms. It could be that those of us with eczema are descended from a population that was under severe evolutionary pressure from parasitic worms. These worms are no frickin' joke-- look up "elephantiasis" or "river blindness" if you can stomach the photos. I don't know about you, but I'd rather have eczema.

I'm guessing that I and my family have extrinsic AD. Naturally, that's the kind I'm interested in!-- but, knowing all too well what it's like to live with eczema, I'd like to see all of us cured.

I'm not naive, either-- I know eczema is fiendishly complex and there's no cure at the moment. It may turn out that we won't see a cure for hundreds of years. It may turn out that the only way to prevent eczema is gene therapy in embryos. It may turn out that you can reduce symptoms dramatically by rubbing your baby with a certain type of protective cream to prevent allergen entry through the skin, and that if you do this during a certain time window, the protection will extend to adulthood. It may turn out that we can't fix anything fundamental, but that we can turn off itching and scratching by using some miracle drug that gets discovered completely by accident. (And, likely, the drug will only work for a certain fraction of people-- but maybe we can identify them by genomic screening.)