Tag Archives: allergy

Dung hill counting

Wikipedia writes about Imre Lakatos the famous Hungarian mathematician and philosopher who graduated 1961 in Cambridge with “Essays in the Logic of Mathematical Discovery”

He showed that in some cases one research programme can be described as progressive while its rivals are degenerative. A progressive research programme is marked by its growth, along with the discovery of stunning novel facts, development of new experimental techniques, more precise predictions, etc. A degenerative research program is marked by lack of growth, or growth of the protective belt that does not lead to novel facts.

 

One of these degenerate research program relates to the hypothesis that farming protects you from allergy

E 2006:

There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role … Both atopic sensitization … and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects … Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16

Keep in mind – it’s the farm animal.

K 2008:

Several epidemiological studies have shown that the farm environment impacts allergy protection mechanisms in children … In investigating the link between farming lifestyle and prevention of childhood allergy, we examined the prevalence of Listeria spp. in dust specimens from the environment of rural children … The dominant species found by culturing methods were L. innocua (n=12) and L. monocytogenes (n=8).

Sorry – it’s listeria.

K 2006:

There is increasing evidence that the farming environment has a protective effect as regards allergic diseases. Exposure to animal parasites, particularly helminth infections, is common in the farming environment. Exposure to nematodes, as determined by the levels of antibody to A. lumbricoides, was more frequent among farmers’ children than non-farmers’ children… This positive serology was found to be significantly associated with high total IgE levels … and eosinophilia.

Sorry again – it’s ascaris.


E 2007
:

In recent years, studies have shown a protective effect of being raised in a farm environment on the development of hay fever and atopic sensitization…Inverse relations with a diagnosis of asthma were found for pig keeping …, farm milk consumption …, frequent stay in animal sheds …, child’s involvement in haying …, and use of silage … Protective factors were related with higher expression levels of genes of the innate immunity.

Sorry, it’s everything: the pig, the milk, haying and silage.

W 2007:

Some studies in rural environments claimed an inverse association between consumption of farm-produced dairy products … Farm milk consumption ever in life showed a statistically significant inverse association with asthma… rhinoconjunctivitis … and sensitization to pollen and the food mix fx5 …, and sensitization to horse dander.

Hey, milky ways ahead something new: the horse!

K 2007:

There is still uncertainty about the determinants of atopic eczema … In multivariate analyses, helping with haying was the only variable related to a farming environment having a consistent inverse association with both current symptoms and a doctor’s diagnosis of AE.

Yes,  haying makes sense with hayfever.

W 2005:

An increasing number of studies report pet exposure to be associated with lower risk of asthma and allergies … Current contact with dogs was inversely associated with diagnosed hay fever (OR 0.26, 95% CI 0.11-0.57), diagnosed asthma (OR 0.29, 95% CI 0.12-0.71), sensitization…

Oh no, the dog.

V 2008:

Numerous epidemiologic studies have demonstrated an allergy-protective effect of farm life early in childhood …In vitro, B. licheniformis spores activated a T(H)1 cytokine expression profile. In vivo application of these spores resulted in less spore-specific but long-lasting immune activation preventing eosinophilia and goblet cell hyperplasia; however, they provoked an influx of neutrophils in lung tissue of asthmatic mice.

What about bacillus spores?

vM 2008

Contact with farm animals, at least in childhood, likely confers protection; other factors have not been completely identified. Also, the consumption of milk directly from the farm during childhood has been shown to be beneficial with respect to childhood asthma and allergies.

Ok, it is milk. Are you still readings here?

This week I am back with the most exciting research

Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school age … Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow’s milk independently from maternal IgE.

This paper counts dung hills The authors even invent a new classification (sorry, not dung hill height but “50 m distance between dung hill and house”).

And did you also wonder why paternal history is no more a risk in thesel studies? There are only a few allergic parent due to healthy worker effect…
No adjustment for multiple testing “because it will lead to fewer errors of interpretation when the data under evaluation are not random numbers but actual observations on nature” That is one of the most stupid sentences I have ever read.

The overall response rate in this study is 32% and the strongest risk for cord blood IgE is maternal IgE. Is there any statistical model that can account for poor data by contamination of newborn cord blood with maternal IgE? And uhh, 32% response is that really a representative sample?

Did you notice that being a farm child now suddenly becomes a risk for seasonal sensitization (OR=1.18, NS) and food allergy as well (OR=1.25, NS)? And that farm milk consumption is suddenly a risk! for IgE to cow’s milk (OR=3.64, p=0.01)?

The mantra at the beginning at each of the abstract above is certainly necessary to let us believe in the rest of these papers.

Addendum 8/8/2008
Poster E3269: Prenatal exposure to a farm environment affects atopic sensitization at birth at ERS Berlin Tuesday, October 7, 2008.

Furthermore, inverse associations of CB IgE to seasonal allergens with positive maternal records for Toxoplasma (T.) gondii (adjusted odds ratio = 0.37 [0.17-0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13-0.96]) were found.

gotcha – Toxoplasma + Rubella.

Addendum 11/12/2009
a new paper & a new cowshed derived bacterium: Acinetobacter

Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis.

Addendum 28/2/2011
a new press release Eurotium

Mikrobielle Vielfalt allein reicht vermutlich allerdings nicht aus, um Asthma zu verhindern. Wahrscheinlich ist es eine Kombination spezifischer Arten, die eine Schutzwirkung entfalten kann. „Im gesamten untersuchten Spektrum fanden sich einige Keime, die besonders interessant sein könnten”, berichtet Ege, „dazugehören außer bestimmten Bazillen und Staphylokokken – etwa die Art Staphylococcus sciuri – auch Schimmelpilze der Gattung Eurotium.“

Addendum 1/1/2018
The research above has now lead to the highest German Science Prize, an honorary doctorate, an ERC advanced grant, a Leopoldina and Bavarian Academy membership.

 

CC-BY-NC Science Surf accessed 05.11.2025

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

 

CC-BY-NC Science Surf accessed 05.11.2025

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

 

CC-BY-NC Science Surf accessed 05.11.2025

Allergy starts only after birth

Although there are numerous reports and even whole schools of thought building on a prenatal origin of allergy, a new study now clearly states that sensitization does not develop in utero. IgE traditionally measured in cord blood IgE is a contamination of maternal IgE. The authors show that there is a correlation with IgA and the “spurious specific IgE” at birth “vanishes” during the following 6 months. If you ever had a cord in hand, you will understand how easily contamination occurs.

Addendum 12/10/2008

The “prenatal origin” party doesn’t give up basically with the arguments:

  • no Ig A found that would be indicative of contamination BUT unfortunately their Ig A threshold of 32 ug/mL is not really appropriate
  • more than half of their cord blood samples have IgE negative mothers BUT unfortunately they don’t show the unclassified IgE values (is that’s just an artifact of a normal test variation?)
  • some of their cord blood samples have higher IgE levels than the mothers BUT again the same argument of an arbitrary classification applies
  • most single IgE results are not concordant between mother but they admit concordant results at least for food allergens. This may indeed been taken as an argument against simple cord blood contamination of ALL samples. As the accompanying editorial points out an in vivo translocation of immune complexes of IgG:allergen+IgE of a food allergens (that are nearly always present in contrast to some seasonal allergens) may be possible
  • the discussion ignores more or less the fact that there is definitely NO concordance with the father (as shown in table I) so leakage or contamination is likely

The authors explain the maternal/fetal association “by maternal inheritance of atopic IgE responsiveness on chromosome 11q and other gene loci” BUT unfortunately there is neither atopic IgE responsiveness on chromosome 11q nor is there any evidence of imprinting. So – according to our best evidence allergy starts only after birth. To convince me it would not need 922 neonates but 1 B cell of proven fetal origin that makes IgE – making the whole story at least a good example how insufficient methods produce doubtful conclusions, yea, yea.

 

CC-BY-NC Science Surf accessed 05.11.2025

Severe flaw in mouse allergy studies

A report in Biospektrum 07.07/13:762 about the production of endotoxin free ovalbumin by a German company now reveals that nearly all commercially available ovalbumin preparations are highly contaminated with endotoxin. Company A included 723, company B 1038, company C 257 and company D 342 EU/mg LPS. As all mice are usually also on a vitamin D supplement diet, recent mouse studies may have produced largely artifacts if both – agonist and antagonist – are included in an uncontrolled manner, yea, yea.

 

CC-BY-NC Science Surf accessed 05.11.2025

Best allergy paper 2007

The end of the year 2007 is approaching very fast. I can already vote for the best allergy paper in 2007 – it is a paper from Vienna by Victoria Leb about the molecular and functional analysis of the Ambrosia antigen T cell receptor. They have been able to isolate and transfer alpha (TRAV17-TRAJ45) and beta chain (TRBV18,TRBD1 and TRBJ2-7) TCR chains into Jurkat cells and even other human blood lymphocytes with convicing evidence that the infected cells were Ambrosia Art V1 reactive.
This opens brand new perspectives for developing a truely allergic TCR transgenic mouse that can be easily challenged and desensitized. It may even allow immediate testing of a variety of substance (and constructs) to ultimately cure allergy. My favorite is to feed DCs with antigen coupled to a T cell suicide program on succesfull antigen presentation.

 

CC-BY-NC Science Surf accessed 05.11.2025

Auto desensitization

Blackley found already in 1873 an interesting explanation of the “no allergy in farming children” effect by referring to some kind of auto desensitization in this particular environment – e.g. the high pollen and LPS exposure.
Do you know that a commercial allergen preparation used for desensitization already includes a LPS derivate, 3-o-desacyl-4′ monophosphoryl lipid A as an adjuvant? It is believed to push the pollen reaction into a IL12 – IFNg – Th1 pathway. This therapeutic approach already perfectly fits the early explanation of Blackley.
When will the allergy farming lobby ultimately close their files?

 

CC-BY-NC Science Surf accessed 05.11.2025

Vitamin A and allergy

No, I am not confusing here vitamin A and vitamin D as done in the early days of vitamin research. This post is really about vitamin A (but with similar nomenclature problem as with vitamin D). Retinol is ingested in a precursor form; animal sources like liver (–>cod liver oil) contain retinyl esters, whereas plants like carrots contain carotenoids. Continue reading Vitamin A and allergy

 

CC-BY-NC Science Surf accessed 05.11.2025

Time to give Blackley the credit he deserves

I am currently doing some historical studies if the vitamin hypothesis fits also the temporal relationship of allergy prevalence. While ordering RKI files for my next trip to the Berlin document center, I found that farming and lower allergy sensitization is known much longer than I anticipated. Continue reading Time to give Blackley the credit he deserves

 

CC-BY-NC Science Surf accessed 05.11.2025

Allergy transplantation

A new paper in Transplantation takes up an old question – can you passively transfer asthma or allergy? It seems so – the current study reports in 5 of 42 patients elevated IgE plus allergy symptoms. This is in line with earlier reports. Sorry to say — you can get allergy also by bone marrow transplantation.

 

Addendum 10/6/08
Blood

A total of 16 nonallergic recipients with allergic donors were reported to develop allergic disease posttransplant, however, conclusive information was available for only 5 cases. Allergic disease was reported to abate in 3 allergic recipients with nonallergic donors, however, conclusive information was available for only 2 cases. Problems in interpreting the reports include incomplete data on allergic disease in the donor or recipient pretransplant, not knowing the denominator, and the lack of controls. In summary, review of the literature generates the hypothesis that allergic disease is transferable

 

Addendum 14/7/22
Ann All Asthma Immunol

 

CC-BY-NC Science Surf accessed 05.11.2025