Here is an interim update on some genes of my recent asthma exome paper coming now from 1 M exomes published yesterday in a preprint.
loss of function variants IL1RL1. https://rgc-mcps.regeneron.com/gene/IL1RL1, 12 May 2023
Also ClinVar shows that the IL33 receptor is not “essential” making anti IL33 receptor antibodies like etokimab, itepekimab, tozorakimab a safe therapy although not being effective in the many LOF mutation carriers.
The most interesting thing in the preprint is in supplemental table 2 with all the s-het values for 16,704 genes. From that table I have selected my favorite target IL33 receptor together with TLR1, ALOX15, GSDMA, IL13 and IKZF3. Only BTNL2 could not be found.
asthma exome https://rgc-mcps.regeneron.com/gene/IL1RL1, 12 May 2023
IKZF3 would be dangerous to be touched (see my 2008 commentary) while in the 2022 exome paper I found only protective variants in the 5′-UTR but not any LOF variant in IKZF3- probably as it is the only essential gene when looking at 1 M exomes.
report the impact of COVID‐19 lockdown in 365 Irish babies at 6 months of age enrolled in the CORAL study. These were a subset of 3773 infants born in two participating major maternity hospitals in Dublin between March and May 2020. Unfortunately only 10% of children participated, so families were self-selected. Allergic rhinitis was common in both mothers (36%) and fathers (30%) which is higher than reported by Allergy Ireland (26%) and explained by the authors that parental allergy is “higher than the general population, which may have contributed to parental desire to enrol in this study.”
A follow-up in March 2022 in 344 children consecutively shows higher food allergy (4.7% vs 3.5%, NS) when compared to an earlier cohort (BASELINE 2008). Atopic dermatitis increased of 15.5% in the BASELINE study to 25.3% in CORAL (no P reported) which is not unexpected given the interest of parents in an allergy study.
Maybe a short questionnaire at 2026 school entry would be informative than the current study? Nevertheless the authors needed now to analyze their stool samples sitting in the shelves. This is the content of the March 2023 preprint that has just been published. There may be an association of some bacteria with atopic dermatitis but in the end it is a useless result as the strongest risk factors for atopic dermatitis – parental history and/or FLG mutations – are missing from the presented models
At the end we can safely assume that the 2020 lockdown did not have any influence on allergy prevalence in Ireland.
Remarkable progress has been made in somatic human genome editing, demonstrating it can cure once incurable diseases. To realise its full therapeutic potential, research is needed to expand the range of diseases it can treat, and to better understand risks and unintended effects. The extremely high costs of current somatic gene therapies are unsustainable. A global commitment to affordable, equitable access to these treatments is urgently needed. Heritable human genome editing remains unacceptable at this time.
And well, my subjective selection of the best talks is also here (unfortunately the video quality is poor and there is no way to timestamp the URL, so you have to recall the time marks below).
As always masterful moderation by Robin Lovell-Badge including the fire alarm ;-) My top 5 talks are
(Jennifer Doudna 4:25:17 was a bit disappointing when talking about my research field involving asthma and microbiome.
The two father mouse of Katsuhiko Hayashi that gained wider attention [Guardian, Nature, …] is found at 3:14:02.
Cheung and colleagues reports a survey conducted in 15 countries exploring the health and nutrition claims made in the marketing of infant formula products. The authors performed a systematic search of websites, examined packaging of formula products, and documented claims made about the formula product and citations of scientific evidence supporting those claims…
Health professionals and families lack the time to properly scrutinise claims. Industry is unlikely to change its practice given shareholder interests. Self-regulation has not worked, and responsible, ethical marketing by the formula industry seems unlikely.
Ich hatte direkt nach der Wende in Halle und Leipzig die erste Ost-West Allergiestudie* durchgeführt und dabei die verblüffende Entdeckung gemacht, dass es im Osten nicht mal halb so häufig Allergien gab.
Der Grund dafür war uns zunächst nicht klar, aber dann stelle sich doch bald heraus, daß es wohl die unterschiedliche Vitamin D Prophylaxe war – im Westen gab es tägliche niedrige Dosen ab der ersten Lebenswoche, im Osten wurde ab dem 2. Monat wenig hohe hohe Einzeldosen verabreicht. Wenn Kinder im Osten krank waren, dann fiel auch immer wieder die eine oder andere Dosis aus, auch wurde das Schema nach meiner Recherche nicht immer komplett durchgezogen. Leider haben wir uns damals aber nur die Impfpässe angesehen, nicht aber die im Nachinein wichtigeren Wiegekarten.
DDR Wiegekarte. Quelle https://www.ddr-museum.de/de/objects/1011262Westdeutsches Untersuchungsheft U2. Quelle https://www.g-ba.de/downloads/83-691-452/2017-05-11_GBA_Kinderuntersuchungsheft_Web-WZ.pdf
Die Befürchtung der Professoren Mai und Beuren in dem alten SPIEGEL Artikel über Vitamin D Nebenwirkungen haben sich zum Glück nicht bewahrheitet. Dafür aber stellte sich dann aber eine unerwünschte immunologische Wirkung heraus die damals noch nicht bekannt war.
Mit dem aus England bzw Amerika importierten Schema zur Supplementierung stiegen die Allergien an. In der BRD war das ab den frühen 60er Jahren , wie überhaupt die englischsprachigen Länder immer die höchsten Allergiehäufigkeiten hatten, da sie wegen der häufigen Rachitis auch viel konsequenter supplementierten (die Rachitis hiess früher einmal auch “englische Krankheit”).
Der Mechanismus der Allergieentstehung ist dabei nur teilweise aufgeklärt: Vitamin D ist jedenfalls immunsuppressiv mit vielfacher Auswirkung auf B und T Zellen was seit dem Nachweis des Vitamin D Rezeptors auf diesen Immunzellen wissen. Die Supplementierung stört offensichtlich die initiale Klassifikation ob ein Protein harmlos oder allergen ist.
Warum es aber auch schon 1989 Allergien im Osten gab? Nun, es war ja keine Vitamin D freie Zone, offensichtlich sensibilisiert man sich auch noch ausserhalb des überkritischen Intervals in den ersten Lebenswochen.
It seems that I missed an interesting 2017 paper that looked for disease-associated SNPs in canonical DR3 motifs. Only 7 out of 211 traits showed significant hits, one of these was self-reported allergy. When annotating these SNPs, there are only two genes: LINC00299 and TLR1
So are TLR1 & LINC00299 variant carriers more susceptible to vitamin D induced allergy?
LINC00299 (Long Intergenic Non-Protein Coding RNA 299) is a RNA Gene of largely unknown function, associated so far with allergy only on a genetic level in Framingham, href=”https://pubmed.ncbi.nlm.nih.gov/23817569/”>23andme and other studies. We don’t know so much here, the function of the long non coding RNAs
depends on subcellular localization. Depending on their niche, they specifically interact with DNA, RNA, and proteins and modify chromatin function, regulate transcription at various stages, forms nuclear condensation bodies and nucleolar organization. lncRNAs may also change the stability and translation of cytoplasmic mRNAs and hamper signaling pathways. Thus, lncRNAs affect the physio-pathological states and lead to the development of various disorders, immune responses, and cancer.
The TLR1 genetic association is found by many genetic studies, while the clinical association is probably more by an infectious origin. TLR1 is a pattern recognition receptor with a specificity for gram-positive bacteria and also included in my forthcoming exome paper as a protective factor for asthma/allergy. And we are also close to my earlier review of vitamin D, the microbiome and allergy…
Does any co-infection response during first vitamin D exposure influence allergic sensitisation? There are indeed some hints of an short-lived effect of lung group 2 innate lymphoid cells (ILC2s)
Laboratory mice cohoused for 2 weeks had impaired ILC2 responses and reduced lung eosinophilia to intranasal allergens, whereas these responses were restored in mice cohoused for ≥2 months. … These findings suggest that ILC2s respond dynamically to environmental cues and that microbial exposures do not control long-term desensitization of innate type 2 responses to allergens.
I have criticized in the past the milk industry sponsored research that is now operating at a similar scale like research funded by cigarette industry [1]. And well, it seems that I am not alone here when reading a new CEA paper “Are paediatric allergy services promoting or harming public health?”
There were increasing and excessive sales of specialized formula designed for infants with milk allergy—either extensively hydrolysed or amino acid formula. These represented 7.6% of formula sold in 2019 … Although pediatric allergy services cannot be held solely to blame for whole population trends, there is evidence that the clinical guidance used in pediatric allergy clinics might promote or exacerbate these trends. Moreover, many allergy, gastroenterology and pediatric societies and professionals routinely flaunt public health guidance from the World Health Organization by continuing to accept funding from formula companies, despite World Health Assembly resolutions that such conflictive relationships should be avoided.
Unfortunately there are now also many asthma trash papers from paper mills. Another example was identified by @gcabanac, distributed by @deevybee and published at Pubpeer.
In total there are 386 asthma entries at PubPeer. What is really happening in this field? When I started the field there was just one misconduct case – Ranjit Kumar Chandra. That’s an increase from 1 to 386…
What makes it even more complicated that there is no border anymore to predatory journals if also respected scientists drop their names at predatory journals. Only recently I received an email addressed to one of my former technical assistants as “professor” inviting her to send a paper…
Schön jedenfalls die vielen juristischen und historischen Einordnungen in diesem Twitter Thread. Es fehlt dabei nur Grafton
Die Fußnote, besonders die deutsche, wird oft für den Inbegriff langweiliger Wissenschaft, für einen Geheim-Code trockener akademischer Gelehrsamkeit gehalten. Doch das heißt, sie als Tummelplatz der Leidenschaften, als Schlachtfeld intellektueller Kämpfe zu verkennen. Anthony Grafton ist es unter Einsatz von zahlreichen Fußnoten gelungen, neues Licht auf ihr Schattendasein zu werfen und ihre dramatische Bandbreite darzulegen.
Geisteswissenschaftler lächeln gerne über den vermeintlich naiven Objektivismus der Naturwissenschaftler. Dabei ist die Geschichte der Naturwissenschaft der geisteswissenschaftlichen Konkurrenz in der Kritik der wissenschaftlichen Denkformen weit voraus. Thomas Kuhn regte Chemiker und Physiker an, nach der Geschichte von Versuchsanordnungen und Beweisverfahren zu fragen.
Again: The hygiene hypothesis was not born by David Strachan and well, there are more cracks of the hygiene hypothesis.
“The trouble is, as soon as you use the words ‘hygiene hypothesis,’ the word hygiene prejudges what the cause is,” says Bloomfield. To the public, “hygiene” is interpreted as personal cleanliness: washing hands, keeping food clean and fresh, sanitizing the home. However, because the hypothesis has been largely uncoupled from infections, the idea that we need to be less hygienic is wrong. Relaxing hygiene standards would not reverse the trend but only serve to increase the risks of infectious disease, says Bloomfield. The term “hygiene hypothesis” also fails to incorporate all of the other factors now linked to the increase in immunoregulatory diseases.
I expect that five years after mandating “super hygiene” during COVID-19 we can finally bury the hygiene hypothesis.
Just tried citationgecko.com on a topic that I have been working on for 2 decades. It will find rather quickly the source paper, much faster than reading through all of it. Unfortunately reviews are rated to be more influential than original data as Citation Gecko picks articles with many references.
Please see also an earlier comment on image duplications: While results do not change if authors are repeating images of the same object without notice, this is not providing independent evidence and therefore affecting the conclusions.
JACI is the journal with the poorest experience that I ever encountered as an author and as a reviewer. The editors never adequately responded to numerous errors in an earlier paper where I sent a long letter describing all details.
