Tag Archives: allergy

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

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.

Vitamania

For everybody who wants to follow up the most recent discussion about allergy promoting effects of vitamin D here is a short summary. The Harvard group basically wrote three articles that were immediately contradicted. The comment on the first article in JACI was by a NIH researcher Continue reading Vitamania

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.

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.

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?

No proof of hygiene hypothesis

Yahoo News writes “Doubts cast on hygiene hypothesis“. As far as I know YN highlights the first experimental study of the hygiene hypothesis. Although the authors could achieve a reduction of respiratory infections by controlled randomized hygiene intervention, there was no effect on later asthma or allergy.

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

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

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

Notes on asthma in Africa

I have just found our most recent PLOS paper about asthma in Africa being published online

As of the 1980s, there was an overall conviction that asthma had an anthropogenic origin with indoor and outdoor air pollution as the main culprits. Following some overinterpreted epidemiological findings of the “hygienic” phase, there is now evidence accumulating that the asthma epidemic might have an iatrogenic origin. There might not only be indirect effects of improved living standards and better medical care, there are even direct effects under discussion, for example by oestrogens, vitamin D, antibiotics, and paracetamol. Infant formula (which contains vitamin D) has already entered the food chain in Africa; paracetamol is the most common drug bought over the counter in Ghana. Do African countries offer any unique observations where singular effects of these drugs can be delineated?

An independent review (that I did not know at time of writing) arrived at similar conclusions. We all, however, forgot to mention sensational news as Gambian president Yahya Jammeh can heal asthma clickclick – a more serious appraisal click.

My childhood favorites
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Unripe

A key event in the vitamin D hypothesis of allergy induction is the immature state of dendritic cells. So far, maturity has been mainly described in terms of reduced expression of cell surface marker like CD80. A new study in Nature now further unravels how the capacity of DC to present antigen may be disturbed. Ubiquitination – the covalent attachment of ubiquitin polymers – of the MHC II ß chain ceases on maturation allowing the transport from endosomal compartments to the plasma membrane. Immature cells seem to be capable to some level of peptide-MHC interaction (at least for some selected antigens) although this process is greatly enhanced by maturation of DCs. Semi-maturity is believed to be an important inetrim stage where at least an earlier review argued

we propose a model in which steady-state migration and partial maturation (semi-maturation) of DCs is embedded as a major component within immune homeostasis, established for permanent and active tolerance induction against self-antigens derived from peripheral tissues by inducing antigen-specific CD4+ Tr cells. Semi-maturation induced by proinflammatory cytokines, such as TNF-alpha, seems to represent a unique developmental tolerogenic stage for DCs, which is based on the absence of proinflammatory cytokine production, despite high expression of MHC II and costimulatory molecules.

Another interesting study in the J Immunol – coined “alternatively activated dendritic cells” the authors probably talk about the same immature cells (compare with my cartoon summarizing a 2002 paper in Trend Mol Med). These immature DCs secrete high levels of IL10 (a paradox discussed in my most recent paper). In addition these DCs produce low amounts of IL12p70, TLR4 and CCR7. What was new to me, was an impressive list of pharmacological agents that suppress DC development: aspirin (also paracetamol?), corticosteroids, cyclosporine A, rapamycin (also other antibiotics?), and finally mycophenolate mofetil.

There is also an update of the IL10 paradox: Allergic sensitization may be down regulated by CD40 AGONISTs independent of IL10!

Finally, I would like to understand what immature really do after encountering allergen exposure. A new paper in nature immunology says that

immature DC are also thought to carry antigen to lymph nodes and to interact with naive T cells but without a previous maturation stimulus, those interactions result in abortive activation of the T cells, which can be eliminated, rendered unresponsive or induced to differentiate into regulatory T cells.

which still does not answer my question.

Vitamin D actions
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Yea, yea.

Some are hybrids, some are not

Microchimerism is an interesting phenomenon that describes the hosting of foreign cells in an individuum – the prefix micro relates to the rather low counts of foreign cells (see the self discussion).
It is believed (but unproven) that most cases of microchimerism relate to the persistence of fetal cells in the maternal organism. The background of microchimerism is extremely complicated as highlighted in a recent review about the immunology of placentation in mammals. This paper has some nice cartoons about the types of placentation (epitheliochorial, endothelichorial and haemochorial) where the invasive potential of fetal trophoblast cells is the culprit of reciprocal (?) cell traffic between mother and fetus. The highest risk is found in women with induced abortion; cell count is ranging from 0 to 21 male cells per 100,000 female cells in peripheral blood; transfer may occur from mother <-> child, twin <-> twin, or sib <-> mother <-> sib.
Microchimerism has been examined in transplantation medicine (where the recipient replaces the outer donor organ epithelium), in blood transfusion and HCT, as well as in some autoimmune diseases (systemic sclerosis, SLE, thyroiditis, PBC). A clinical review reports that fetal cells have been found to persist for many years, probably for a lifetime.
I have doubts if that is true as I am not aware of any quantitative long-term study. Nearly all studies identified only male cells in women although now genomic studies of single cells are possible allowing a much better identification of foreign cells. If you are looking for a PhD thesis, microchimerism could be your field!
I already wondered if microchimerism could lead to genotyping errors, a question that can now easily be tested on the garbage of genotyping labs: We usually have genotyping errors in the 1-10 o/oo range; sometimes we see also triallelic SNPs. As far as I can renember, microchimerism has never been analyzed in the allergy field, although allergy can transplanted as well as asthma. Yea, yea.