Monday, 20 January 2020

Trigger warning Pseudomonas

I eat a lot of bread. I eat more or less every crumb of sourdough that I bake: possibly because it is so tart nobody else will. I do a line in chapattis as well; using 85% wheatmeal flour, known on the subcontinent as Atta. The latter is ridiculously quick and simple; while the sourdough is hard work involving kneading, proving, knocking back, sticky fingers and an over-night of elapsed time. If I couldn't eat bread [and flapjacks, cookies, stollen, cake, shortbread] my quality of life QALY would plummet: rice isn't the same thing at all at all. There is a lot of wheat intolerance out there, even when you discount the neurotic foodies who think that spelt has no gliadin. It has! and here is the sequence of one such protein:
>A0A1P8DTE7_9POAL Alpha-gliadin OS=Triticum spelta 
MKTFLILALLAIVATTATTAVRVPVPQLQPQNPSQQQPQEQVPLVQQQQFPGQQQQFPPQ
QPYPQPQPFPSQQPYLQLQPFPQPQPFPPQLPYPQPQSFPPQQPYPQQQPQYLQPQQPIS
QQQAQQQQQQQQQQQQQQQILQQILQQQLIPCRDVVLQQHNIAHASSQVLQQSTYQLLQQ
LCCQQLLQIPEQSRCQAIHNVAHAIIMHQQQQQQEQQQQLQQQQQQQLHQQRQQPSSQVS
FQQPQQQYPSSQVSFQPSQLNPQAQGSVQPQQLPQFAEIRNLALQTLPAMCNVYIPPHCS
TTIAPFGIFGTN
For spelt Triticum spelta and reg'lar wheat Triticum aestivum, gliadin is a storage protein, quite insoluble, ready for emergencies when it can get broken down and recycled. For me and other bakers gliadin is an elastic stringy kind of substance which contributes to my sticky fingers but also forms sheets in the dough that hold the bubbles of carbon-dioxide to make the bread rise. People who are intolerant of wheat are reacting [symptom list do NOT read if hypochondriac] to the presence of gliadin with an inflammatory response: flooding the gut with water [bloating] and diarrhoea] to flush out a foreign substance. It's called c[o]eliac disease, or celiac sprue, or just CeD. You are very unlikely to get CeD, unless you have a genetic predisposition. HLA-DQ2.5+ and/or HLA-DQ8+ are the genetic variants to avoid if you're going all GATTACA on your next GM child. HLA is a determinant of the Major HistoCompatibility (MHC) genes: a super-variable component of the immune system which has evolved to give us an appropriate response to co-evolving pathogens.  Sometimes the immune system can get over-feisty and cause damage rather than clean up the bad guys. We looked at Campylobacter jejuni and how it sometimes triggers the development of Guillain–Barr√© syndrome afterwards. To some folks' immune system, something on the outside of Campylobacter jejuni looks remarkably similar to their own myelin sheath and having done for all the bacteria, the immune cells start to attack the periferal nerves.

You are almost certainly different wrt your HLA variants from the bloke sitting next to you on the bus. Buuuut, there is s good chance that your HLAs will match your baby sister's; which will be handy if she ever needs one of your kidneys. Variation in HLA is a major cause of transplant rejection. The peculiar thing is that some /many people who are HLA-DQ8+never go on to develop CeD and continue to scarf down toast every morning for breakfast with not a bother on them. It has long been suspected that there is an environmental trigger which kicks off the symptoms of celiac. But it is only now that we have a plausible microbiological culprit. A group of immunologists centred on Monash U. in Australia have published  a paper "T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease" in one of the Nature journals. It's paywalled up the wazoo but they have carefully shown that numerous normal inhabitants of the human gut have proteins which are similar to human gliadin. The enzyme succinylglutamate desuccinylase (PFSGDS) from Pseudomonas fluorescens for starters. But other candidate triggers were revealed in Enterobacter cloacae and Acinetobacter baumanii. The Monash team have done a lot of work to show that the antigens on these normal members of the gut microflora are indeed recognised by T-cell receptors sensitised to gliadin. It's neat because it holds the beginning of a whisper of a clue towards a cure for sprue. Until we're really designing babies you cannot do much about your HLA status - except shake your fist at your cold dead ancestors. And with the crisis of antibiotic resistance you're unlikely to be able to selectively kill all the potential microbial triggers you have in your gut. But you can imagine that a peculiar diet might tilt the balance among your microbial flora so that the trigger-bugs are overwhelmed or driven into hiding

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