Psoriasis as intestinal disease - theory

Mikhail Yuryevich Peslyak,
Nikolay Gavrilovich Korotky.
Psoriasis as netopathy. Model of pathogenesis with unique netosis role. e1.3 edition,
M.: Antipsoriatic Association
"The Natural Alternative", 2021. - 75 pages.
ISBN 978-5-905504-08-2

Electronic Publication Date of first edition e1.1: 2020, Dec 8.
DOI of latest version: 10.5281/zenodo.4310085

Supplements (latest version):
DOI: 10.5281/zenodo.4310106

An analytical survey of results of experimental and theoretical works on psoriatic disease has been carrried out. A new YN-model of pathogenesis of psoriasis as skin manifestation of systemic psoriatic process SPPN is formulated.
The central subprocess of systemic psoriatic process SPPN is PAMP-nemia, namely chronic kPAMP-load on blood phagocytes, also leading to increased kPAMP-level in blood.The key PAMP (kPAMP) are LPS (lipopolysaccharide), PG (peptidoglycan), including PG-Y (peptidoglycan of presumed psoriagenic PsB) and bacDNA (bacterial DNA).
The main reasons of PAMP-nemia are increased small intestine permeability for bacterial products and/or increased level of specific SIBO (small intestine bacterial overgrowth).
PAMP-nemia causes increased kPAMP-carriage of phagocytes and growth of prenetotic neutrophil fraction in blood. SPPN severity is proportional to total kPAMP-load on blood phagocytes and to their total (PG-Y)-carriage. SPPN severity predetermines possibility of initiating and supporting psoriasis.
PsB – bacteria presumed psoriagenic – are given a definition based on existence of genes responsible for forming peptidoglycan interpeptide bridges, similar to Str.pyogenes. All known such species are identified.
Because of PAMP-nemia senescent kPAMP+ blood neutrophils do not completely degrade kPAMP as they preserve the latter for delivery into bone marrow. Many of such neutrophils become attracted into inflamed skin, undergo netosis, and kPAMP (including PG-Y) appear in extracellular space.
Dermal monocytes and dendritic cells endocyte PG-Y, then they transform to maDC-Y (mature DC processing and presenting Y-antigen) and carry out Y-antigen presentation to specific TL-Y, activating them. Skin immune system interprets Y-antigen presentation as a sign of dermal PsB expansion and turns on one of its protection mechanisms – epidermal hyperproliferation.
Pinpoint psoriatic plaque is initiated during dermal inflammatory process L2, causing innate response, particularly at L2(DEMP) - dermal expansion of commensal microbiome with PsB. For L2(DEMP), a phase-by-phase initiation of pinpoint plaque and of its subsequent growth is constructed. Y-priming level (presence and concentration of Y-specific T-lymphocytes in prepsoriatic dermis and lymphnodes) determines possibility of plaque initiation.
Severity and growth of plaque is determined by intensity of Y-antigen income to dermis inside kPAMP+ phagocytes. New kPAMP+ phagocytes and Y-specific T-lymphocytes are constantly attracted into plaques, which supports inflammatory reaction. With decrease of SPPN severity, natural remission of plaques occurs, up to their total disappearance.

Nikolay Korotky, Mikhail Peslyak (2020).
Blood Metagenome in Health and Psoriasis.
Front. Med. 7:333.
doi: 10.3389/fmed.2020.00333

Supplementary Material
for this article can be found online here: 

Supplement S1. Comparative characteristics of 16S and WMS-tests.

Supplement S2. Resources of metagenomic research and sequencing.

Supplement S3. Main researches classification and comparison.

Supplement S4. Income of bacterial products into blood flow from small intestine.

Supplement S5. YN-model of psoriasis pathogenesis. Partial description.

A survey and analytical assessment of the results of fundamental works on studying blood metagenome (set of all non-human DNA) is carried out. All works on determining bacterial DNA concentration in the whole blood of healthy people are reviewed. Detailed comparison of characteristics of 16S rRNA test (hereinafter 16S-test) and whole metagenome sequencing test (hereinafter WMS-test) is carried out and published in Supplement S1. One of main goals of this review is to identify the drawbacks and mistakes which the studied works contain, particularly to emphasize the crucial importance of determining total concentration of bacterial DNA for comparing patients' metagenomes with those of healthy people as well as for comparing patients' metagenomes with each other. Controlling the level and composition of contamination is equally important. The absence of high-quality contamination control at each step (or at certain steps) of the research significantly reduces the reliability of achieved results. The given review is the first attempt to analyze and systematize the results of blood metagenome studies, whose number has increased considerably in the last few years. The review has been carried out as part of preparation for implementing a project on complex studying metagenomes of whole blood and skin biopsies of psoriatic patients.

Mikhail Yuryevich Peslyak,
Nikolay Gavrilovich Korotky.
Metagenomes of blood and psoriatic skin. Research project. e2.2 edition,
M.: Antipsoriatic Association
"The Natural Alternative", 2019. - 67 pages.
ISBN 978-5-905504-06-8

Electronic Publication Date of edition e2.2: 2019, May 7.
DOI: 10.5281/zenodo.2667680

Main supplements:

A. Presentation and illustrations.
(e2.2, DOI: 10.5281/zenodo.2668376)

The first stage of NCS-project devoted to the study, diagnostics and treatment of psoriasis is substantiated and given a detailed description. The purpose of the first stage is testing the basic hypotheses of new systemic YN-model of psoriasis pathogenesis. The test consists in complex studying of whole blood metagenome and metagenome of psoriatic skin (phagocytes). Metagenome is all non-host DNA (here - non-human) which is found in biomaterial. The necessary algorithms for complex studying of metagenomes are suggested and substantiated.
Survey and analytical assessment of the results of fundamental works on studying metagenomes of blood and skin is carried out. All works (published prior to the beginning of 2019) on determining bacterial DNA concentration in whole blood of healthy people are reviewed.
Detailed comparison of characteristics of 16S-test and WMS-test is carried out.
The objectives and tasks (including the order of solving them) of the first stage are formulated. The main questions are raised, to which the results of the first stage are supposed to give answers. The order of preparing and implementing WMS-test of whole blood is suggested.
Detailed comparison of YN-model of pathogenesis with the previously published Y-model is conducted. An analytical review of works on studying the attraction of blood neutrophils in psoriatic skin and their possible subsequent netosis is made. Netosis in psoriatic skin of neutrophils which are carriers of endocytosed Y-antigen in blood is qualified as an essential link in the vicious cycle of psoriatic inflammation within YN-model. Classification of psoriatic disease as netopathy is suggested.
Psoriagenic bacteria are given definition based on the existence of genes responsible for the formation of interpeptide bridges. The smallest peptides (peptidoglycan fragments) - potential Y-antigens are identified.

Mikhail Peslyak, Antipsoriatic Association "The Natural Alternative"
Nikolay Korotky, Pirogov Russian National Research Medical University

NCS-project of scientific research
"Development of new methods of complex diagnostics of metagenomes and microbiomes of throat, intestine, blood and skin of psoriatic patients, and also their corrections for achievement of long and steady remission".
Moscow, 2018
(NCS_summary)

NCS-Pitch
(v1.2, 10 pages, pdf)

DOI: 10.5281/zenodo.1472953

NCS-Presentation (and illustrations for pitch)
(v1.1, 31 slides, pdf)

DOI: 10.5281/zenodo.1473780

Presentation (project)

Psoriasis as skin reaction to systemic psoriatic process SPP.
Y-model of pathogenesis.
(version e2.1, 2012, Jun 17)

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Put pdf-files of presentation and e-books in one directory that these links were functional
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Date of first publication in Internet
version e2.0:
2012, May 2
(stored in archive of previous versions)

Mikhail Peslyak
Model of pathogenesis of psoriasis.
Part 1. Systemic psoriatic process.
MYPE, 2012. - 84 p.
ISBN 978-5-905504-02-0
English edition e4.0 (revised and updated),
Electronic Publication Date: 2012, Apr 14
Download this e-book free (pdf-format)

Date of first publication in Internet e2.0: 2009, Dec 30 (stored in archive of previous editions)

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on Scribd
(read and download free)

This e-book
on Arxiv.org
(download free)

Abstracts to Part 1 and Part 2.
Y-model of pathogenesis of psoriasis.
The summary scheme of dependencies.

Mikhail Peslyak
Model of pathogenesis of psoriasis.
Part 2. Local processes.
MYPE, 2012. - 110 p.
ISBN 978-5-905504-04-4
English edition e1.3,
Electronic Publication Date: 2012, Apr 14
Download this e-book free (pdf-format)

Date of first publication in Internet e1.2: 2011, Dec 28 (stored in archive of previous editions)

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on Arxiv.org
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Reviews from experts about the monograph
"Model of pathogenesis of psoriasis".

June 27 - July 1, 2012,
in Stockholm, Sweden was
3rd WORLD PSORIASIS & PSORIATIC ARTHRITIS CONFERENCE 2012

Next report (P025) was presented
on this conference:
Small intestine microflora at psoriasis. Its possible role in pathogenesis.
(Mikhail Peslyak,
Natalia Gumayunova, Alex Nesterov, Natalia Potaturkina-Nesterova)
This report and supplements are here.

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in one RAR-archive
(copy of free CD)