Category Archives: Allergy

Something in the air

New studies further question the hygiene hypothesis of allergy induction. One study shows that a household bacterial elimination strategy does not lead to more — it even leads to less asthma.

Children living in a house regularly cleaned with bleach were less likely to have asthma (OR, 0.10; CI, 0.02-0.51), eczema (OR, 0.22; CI, 0.06-0.79) and of being sensitized to indoor aeroallergens (OR, 0.53; CI, 0.27-1.02)

Another study, by designing a 16S rRNA chip, examined a snapshot of urban air in San Antonio — the aerosol harbored at least 1,800 diverse bacterial types

a richness approaching that of some soil bacterial communities

You probably know the joke that before taking a deep breath think where the air has been before…

Addendum

The ecology of human skin has now been also reported – highly diverse, well conserved but low-level interpersonal consensus: scienceblog:doi:10.1073/pnas.0607077104

Say no

German Ärzteblatt has some important suggestions “Mehr Mut zum Nein-sagen” how the German healthcare system may be improved. In brief,
(1) patients need to be empowered to make their own health decision – Norwegians have on average only 3 but Germans 16 physician contacs per year
(2) during professional contact patients need more trust in doctor, nurse, pharmacist and physical therapist
(3) more money for the ill, less for the health people

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Asthma – a disease of the gut

When starting in the asthma field in 1989, the textbooks told me that asthma is a disease of the lung. Some years later, asthma turned out to be a disease of the bone marrow cells. More recently, I raised the question if asthma could be even a disease of the gut – our largest immunological organ being frequently exposed to allergen & plenty of immunological active substances. Although on the different track (vitamin A) also other authors now think of an early impaired immune gut response.
Rather unexpected for me was a study in J Steroid Biochem Mol Biol that 1,25(OH)2D3 inhibits in vitro and in vivo intracellular growth of the parasite Toxoplasma gondii. yea, yea.

Genes wanted

The NIH and Jackson ask for nominations of their gene targeting approach (see also A mouse for All Reasons and my previous comment on the 3 R)

KOMP is a trans-NIH initiative to generate a public resource of mouse embryonic stem (ES) cells containing a null mutation in every gene in the mouse genome. Both conditional and null knockouts are being generated. The purpose of this form is to gather input from the scientific community on which genes should have the highest priority for being knocked out.

The Cell paper also explains the hard to understand differences in knockouts

  1. targeted deletion
  2. targeted conditional
  3. trapped conditional

although I still have semantic problems to understand the nomenclature. Anyway my whishlist – you can do me a favor by voting for CYP27B1, VDR, CYP24A1, OPN, IL4, IL5, IL10, IL12, IL13, FLG, CCR5 and CCR9.

Addendum

You can also leave some input at the Environmental Genome Project.

Let vitamin D shine in

said the Denver Post giving a nice overview of vitamin D research. This was just 1 day too early for a fascinating nature immunology paper (scienceblog:doi:10.1038/ni1433:) that links for the first time natural sunlight induced vitamin D action on dendritic cells. Seems that D3 will influence homing of T cells – we are again at “Licht und Leben“, yea, yea.

Addendum

Allergy and DC antigen processing: vitamin versus hygiene hypothesis

Last week Science has an update on differential antigen processing by DCs including a key sentence on immature DCs:

Cultured immature DCs capture antigen but only process and present it on MHC II after exposure to inflammatory stimuli or TLR ligation.

Although the authors were not aware of current allergy research, they perfectly summarize how vitamin D renders DC immature, while hygiene (infections or LPS farm exposure ) may antagonize it.

Science of course and effective too

Most people in the field search Pubmed but there is another site that I frequently visit – the European patent database that often have more concise information. Look at current allergy patents – the last one will definitely work you may also use a big plastic bag ;-)

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Be aware that being cynical is probably bad for your heart.

Beam me up, Scotty, ….

This is the title of an editorial in The Am J Respir Crit Care Med commenting on current asthma research.
Another editorial in the ERJ asks “The human lung: did evolution get it wrong?”
So I am confused: Did pulmonary science or lung evolution (or both) get it wrong?

Banned DNA tests

The Korea Herald writes – as noticed by Hsien Hsien Lei

The government yesterday released a set of new regulations to ban or restrict genetic tests in 20 categories amid ethical concerns over DNA tests … According to the new guidelines, DNA labs will be banned from conducting tests in 14 categories including body mass, intelligence, strength, propensity for violence, longevity, mental health, diabetes, blood pressure and asthma.

Although I do not believe that genetic testing for “asthma genes” will make any sense without the context of scientific studies, I think that such regulations are overdue – at least when genetic testing does not provide any benefit but may pose harm. If you have asthma or not, is a clinical question – and the answer will be an appropriate treatment or not. If you ever will get asthma is a question that nobody can answer. Even if genetic prediction will be ever possible, there is still no preventive measurement (at least by Jan 18, 2006, 16:14:23) . Yea, yea.

Vitamin D and asthma

My previous work on vitamin D focused mainly on allergy but according to new research of Bosse et al vitamin D also stimulates bronchial smooth muscle and airway remodeling

Genetic variants in the vitamin D receptor (VDR) gene were recently associated with asthma. The biological mechanisms explaining this association is unknown, but are likely to involve many cell types given the pleiotropic effect of its ligand … The most significant network of up-regulated genes included genes involved in morphogenesis, cell growth and survival as well as genes encoding structural proteins, which are potentially involved in airway remodelling.

Another study published more or less at the same time by Wittke shows

Conversely, WT splenocytes, Th2 cells and hematopoetic cells induced some symptoms of experimental asthma when transferred to VDR KO mice, but the severity was less than that seen in the WT controls … Lipopolysaccharide (LPS) induced inflammation in the lungs of VDR KO mice was also less than in WT mice. Together the data suggest that vitamin D and the VDR are important regulators of inflammation in the lung…

Innate immunity is species-, individual, organ-specific

In a previous paper I have questioned if LPS

nanogram exposure on the pulmonary epithelium will supersede the gram-wise exposure on the gut mucosa.

This may indeed work as now shown by Eyal Raz in a commentary in Nature Immunology where previous TLR studies

typically reproduce the splenic version of innate immunity (the spleen is used here as a metaphor for the sterile internal environment).

In the lung only the alveolar space is thought to be sterile while macrophages should not be in a constant state of activation (as inflammation would compromise gas exchange).

There are now several indicators for a lung-specific regulation of innate immunity: TLR9 is expressed in human plasmacytoid dendritic cells while TLR4 is only on myeloid DCs; TGFB-ß mediated crosstalk between alveolar macrophages and epithelial cells seems to be unique in the lung; in addition indeolamine induction or surfactant production is not found elsewhere. Yea, yea.

On mice and men with asthma

A new series of pro- and con editorials in the Am J Res Crit Care Med discusses the question why in some instances mouse models have “misdirected resources and thinking”. You may have noticed that I have only rarely used animals for research; the authors of this editorial have collected empirical data on the exploding use of murine models. Despite their attractiveness from a technological point, they are useless because

  • mice do not have asthma as even the most hyperresponsive strain does not show spontaneous symptoms
  • mice do not have allergy – although sensitization can be manipulated by high intraperitoneal allergen/adjuvant injection, this does not involve immediate and late airway obstruction.
  • immune reaction in mice is quite different – the interfering of some substances like vitamin D cannot be reliable tested, there is no pure Th1 and Th2 reaction in human and less stronger IL-13 response
  • mice typically can not be challenged with the complex (and interacting) human exposure – oxidant stress, viral infection, obesity, diet, smoke, pollutants, ….
  • time course is difficult to mimicking in the mouse, there is no longterm model
  • structure of mouse airways is different – there are fewer airway generations, much less hypertrophy of smooth muscle
  • inflammation in mouse is parenchymal rather than restricted
  • humans are outbred, mice are inbred
  • many promising interventions of mice pathways failed in humans (VLA-4, IL4, IL5, bradykinine, PAF,…)

I am sure there are even more arguments – I suggest that the authors have deserved the Felix-Wankel price.

Addendum

15 Dec 06: The BMJ has 6 more examples about the discordance between animal and human studies: steroids in acute head injury, antifibrinolytics in haemorrhage, thrombolysis or tirilazad treatment in acure ischaemic stroke, antenatal steroids to prevent RDS and biphosphonate to treat osteoporosis.
19 Dec 06: Another pitfall paper
31 Dec 06: A blog on animal welfare
25 Apr 07: Call for better mouse models

100 years of allergy

Clemens von Pirquet (1874-1929) was the first to introduce “Allergie” into clinical medicine by characterizing an altered immune reaction of the body to foreign substances. The famous paper was published 1906 in the “Münchner Medizinische Wochenschrift (MMW)” Volume 53, page 1457-1458.

AB Kay published a nice essay on “100 years of Allergy: can von Pirquet’s word be rescued?” that includes an English translation of the above paper. The MMW has a contemporary obituary of Meinhard von Pfaundler (1872-1947) who was one of the earlier directors of the Münchner Haunersche Kinderspital.

Finally, the “Wiener Klinische Wochenschrift” has a CV of Clemens von Pirquet, showing his way to Baltimore and Breslau back to Vienna until his tragic end by committing suicide together with his mentally ill wife.

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Gene lists by automatic literature extraction

Just found at the HUM MOLGEN bulletin board a link to Fable, a new automated literature extraction system. Fable is pretty fast and can output gene lists. Sure, the screenshot below shows only those genes that I mentioned in the abstract, but this is not so bad as the most important genes wil be placed there.
BTW, the number of reviews on asthma genetics have been falling to less than 50% after closing the Asthma Gene Database. Maybe this new service will help to re-establish the former output of reviews ;-) yea, yea.

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IL4 cluster revisited

I am interested in 5q31 and the IL4 cluster since I met David Marsh in the lobby of a hotel in Heidelberg around 1993. David was one of the founding fathers of asthma genetics and I renember how he vividly told me that he has a forthcoming Science paper on the IL4 cluster and IgE. The cluster is still one of the best allergy regions where the signalling through IL4 and IL13 now gets more interest than the work of any of his competitors.
Nature genetics now has an update on the 3-dimensional resolution of the genomic region. It is not cristallographic work as might be expected but a nice study of the chromatin structure that is leading to a coordinated expression of these cytokines. SATB1 (special AT-rich sequence binding protein 1) is thought to anchor specialized sequences letting DNA loops come into interaction. I wonder if there might be even a direct physical interaction of the IL4 and IL13 promotor and if there will be any SNP influencing that interaction? David (who died of brain cancer in 1998) would have really liked this work. Yea, yea.

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