Tag Archives: allergy

IL33, allergy and helminths: Shot in the leg?

Ever since the NEJM paper in 2010 that showed an IL33/ST2 association there are new studies on a daily basis.

Grotenboer 2013 did a functional annotation of the gene and it’s receptor in humans while there is no more doubt about the involvement of IL33 in human allergy.  Right now IL33 suppression is even used as an experimental screening test for allergic reactivity with ongoing phase II studies of anti-IL33 or anti ST2. Good IL33 reviews can be found for example in frontiers in immunology by Tataori et al. or in nature immunology by Smith. These reviews do not tell you so much about the regulation but this has recently elucidated by Gour et al. who describe a tropomyosin–dectin-1 interaction of the human host. Why is tropomyosin such a frequent target of human IgE?

Muscle protein tropomyosin is an important IgE target in a number of nematode infections; Onchocerca volvulus ; Ascaris lumbricoides; Anisakis simplex; and tropomyosin from the blood fluke Schistosoma mansoni is also a human IgE antigen. Tropomyosin is highly conserved across many invertebrates and is responsible for much of the IgE cross-reactivity between Ascaris and dust-mites.

I haven’t found any good  answer to this question. As tropomyosin affects contractility – this seems like “shooting into the leg” of worms whenever they attempt to invade.
Maybe Gour et al. did not know the earlier dissertation from Berlin that already showed a reduced inflammation in the OVA mouse model by administration of recombinant tropomyosin.

The broad cross reactivity to tropomyosin gives rise to the question if helminth tropomyosin could induce allergic reactions to itself and/or tropomyosin of different organisms. Considering the fact that filarial nematodes express tropomyosin on their surface […] and that the continuing turnover of microfilariae confronts the host with relevant amounts of tropomyosin makes this question even more appropriate.

The worm seems to be attacked by anti-worm-surface-tropomyosin IgE whenever the worm tries to invade  the epithelium during an acute infection. During invasion extracellular IL33 is cleaved into a shorter form with enhanced activity attracting more immune cells.
During chronic infestation nothing happens as long as the worm does not invade and doesn’t trigger any IL33 alarmin. As there is continuous tropomyosin antigen antigen contact, the host is slowly desensitzed, clearing IgE in favor of IgG4.

Is this also a model that explains allergy? We don’t know the details but maybe this antigen recognition / response system is being disturbed where allergens like Der p1 mimicking a worm infection by tropomyosin can trigger the allergic reaction in particular as Der p1 a cysteine protease also mimicks an invasion signal.

People who behave fraudently

Richard Smith 3:58 “People who behave fraudently tend to behave fraudently in all aspects of their live”

8:05 “Universities have no interest to discover fraud” 10:42 “Journals don’t have the legal standing” 10:58 “we need some kind of national bodies”

A step forward in allergy research

The most recent paper of my Australian collaborators is a relevant step forward: Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy. Basically they show an

… association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy)… Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels… Low serum 25(OH)D3 level (<50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0; 95% CI, 0.9-38.9) … Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10; 95% CI, 0.03-0.41)… This increases the biological plausibility of a role for vitamin D in the development of food allergy.

Maybe it would be helpful to have also “real” DBP levels for estimating bioavailability (and even data of supplement use) but already the reported results are another strong argument for the vitamin D – allergy axis. This is also largely in line with what I predicted back in 2012

Both vitamin D insufficiency and vitamin D supplementation have been linked to allergy and asthma. This apparent paradox is explained by epigenetic programming in pregnancy by low vitamin D levels and the excessive high supplementation in the newborn period.

Maybe I should have emphasized that genetic variants in the vitamin D pathway are also important for biological effects.

Is this a retraction of the hygiene hypothesis?

There are news about the hygiene hypothesis.

Home cleanliness resulted only in quantitative reduction of floor dust, which mainly indicates removal of superficial dirt with a rather cosmetic effect. Conventional cleaning does not eradicate microorganisms sustainably, because emptied microbial niches are instantly recolonized by ventilation and living carrier.

Sure. Continue reading Is this a retraction of the hygiene hypothesis?

Take care of your last sentence

I have been told long ago to take care of the last sentence in a paper, avoiding any unjustified conclusion or any unwarranted speculation. Let’s start with a fully justified last sentence in the new volume of  “International Nutrition: Achieving Millennium Goals and Beyond

Bildschirmfoto 2014-04-02 um 08.44.39
Bildschirmfoto 2014-04-02 um 08.44.49

It says that Continue reading Take care of your last sentence

Bullet points for future allergy research

Maybe this is a difficult task – defining an agenda for future research. Here are some thoughts as we don’t know the reasons for the allergy epidemic even after 100 years of research. And we don’t have any cure yet, there is some relief of symptoms and there are some limited curative efforts but we don’t have any real understanding of what is going on. The following research areas may therefore be identified in NON-therapeutic research: Continue reading Bullet points for future allergy research

We feel good

If you are writing some kind of online diary your mood is already surveilled by wefeelfine.

However, if you are an allergic patient, you may be interested in a new project of the German Pollenstiftung that runs an online pollen diary. We have pollen counts for a long time but we do not know so much about thresholds and individual variation.
Continue reading We feel good

Shift happens

The current issue of the blue journal has more stuff on the vitamin D hypothesis (that has been shifted recently into the opposite direction). I agree with the editorial that

Intervention studies of vitamin D in the primary prevention and treatment of asthma raise a number of difficult scientific, ethical, and regulatory issues.

That may be true while the editorial includes the widely quoted myth that immunological effects occur only at high doses Continue reading Shift happens

Asthma is a iatrogenic disease

The new Lancet has a paper from our own group as well as another one from ISAAC. We have already suggested earlier that asthma is a iatrogenic disease- the ISAAC paper now confirms at least the long suspected association with paracetamol use – gratulations to my London friend who had been working so long on this hypothesis. The accompanying editorial puts in into context:

Furthermore, although many important potential confounders were included in multivariate analyses, confounding by underlying respiratory disease, differences in hygiene, and use of other antipyretics might also explain the findings.

To put it more on a general level – more iatrogenic factors cannot be excluded, yea, yea.

Not all that wheezes is asthma

A new abstract at the recent ATS congress now clears the 2007 controversy between the Camargo and Gale studies on the effect of vitamin D: Wheezing is not asthma (as the atopy component is missing?). Continue reading Not all that wheezes is asthma

CD 14 now also on the vitamin+allergy list

Just for curiosity I am collecting a list of allergy genes that are vitamin D dependent. The list is already rather long but now there is a prominent addition: CD14. Known as asthma gene for many years the vitamin D dependency isn’t such clear. A clever analysis, however, now shows that there is an intermediate step involved Continue reading CD 14 now also on the vitamin+allergy list

Rough and tumble science

Over the years I have collected a lot of curious hypotheses how allergy develops. Only recently I ended this list as it became rather long – and to be polite – rather useless. Sorry, less polite – but nonsense at its best Continue reading Rough and tumble science

Where is the asthma gene?

A new paper – the second bioinfomatics approach following the groundbreaking work by Perez-Iratxeta – is now coming up with some interesting remarks beyond IL-13 and TGF-ß1 Continue reading Where is the asthma gene?

A factor in hay prevents vitamin D action

As always, a longer literature search prevents from new discoveries… Here comes a nice piece from 1952 on the antagonistic effect of LPS on vitamin D (Is that really LPS or did I interpret it wrong?). Although not included in my recent review on vitamin D and allergy – I attributed the effect to Lyakh et al. – here is the first description of this effect. Continue reading A factor in hay prevents vitamin D action