MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Rizikové faktory a zhoršující prvky

Infections with herpesviruses

Human roseoloviruses

  • Proposed to cause autoimmune disease
  • Defining a causal relationship and mechanism has been difficult
    • Ubiquitous nature of infection
    • Development of autoimmunity long after acute infection

Murine roseolovirus (MRV)

  • Is highly related to human roseoloviruses
  • Neonatal MRV infection induced autoimmune gastritis (AIG) in adult mice
    • In the absence of ongoing infection.
  • MRV-induced AIG was dependent on replication during the neonatal period
    • Was CD4+ T cell and IL-17 dependent.
  • Neonatal MRV infection
    • Associated with development of a wide array of autoantibodies in adult mice
    • Reduced medullary thymic epithelial cell numbers, thymic dendritic cell numbers, and thymic expression of AIRE and tissue-restricted antigens
    • In addition to increasing thymocyte apoptosis at the stage of negative selection
  • Strongly suggest that infection with a roseolovirus early in life
    • Results in disruption of central tolerance and development of autoimmune disease.
  • Increased intestinal permeability (“leaky gut”)
  • Gut dysbiosis
  • Food intolerances
  • Infections (including H. pylori)
  • Long-term use of reflux medications like proton pump inhibitors (PPIs) (evidence is mixed)
  • drruscio.com/autoimmune-atrophic-gastritis/

Helicobacter pylori Inducing Autoimmune Gastritis

  • Infection with Hp can trigger an autoimmune response within the gastric mucosa
  • Around 65% of Hp-infected individuals have detectable levels of autoreactive gastric antibodies (Negrini et al., 1996).
    • Were most frequently specific to parietal cells
    • Increase in autoantibodies positively correlated with gastric disease severity (Negrini et al., 1996; Faller et al., 1997).
  • Hp-infected people with serum-detectable gastric autoantibodies
    • Showed increased corpus atrophy,
    • Decreased stomach acid production,
    • Increases in routine AIG diagnostic markers
  • Hp infection to be associated with a variety of other autoimmune diseases (Smyk et al., 2014).

Molecular mimicry has been suggested

  • Major Hp surface protein, beta urease
    • 72% sequence homology with the beta chain of the parietal cell specific H+/K+ ATPase
    • One possible antigen activating Hp effector cells against gastric tissue (Uibo et al., 1995)
  • In Hp infected patients who developed AIG
    • CD4+ T cells were isolated from gastric biopsies
      • Several clones were cross-reactive against peptides from parietal cells and Hp lysate
      • Stimulation in the presence of both antigens induced T cells to produce large and equivalent amounts of IFN-gamma (Smythies et al., 2000; D'Elios et al., 1997; D'Elios et al., 2001)
    • Cross-reactive cells were differentiated into the
      • Th1 cells typically present in both AIG and Hp-induced gastritis

Hp infection epithelial cells increase antigen presentation capabilities

  • By upregulating MHC II molecules on their surface
    • Increasing the possibility for self-peptide presentation (Archimandritis et al., 2000)

Pernicious anemia

  • Around 60% of pernicious anemia (PA) patients have serologic and/or histologic evidence of Hp infection
    • Close to the frequency found in the general population (Annibale et al., 2000; Presotto et al., 2003)
    • Prevalence among PA patients does not show a correlation between Hp infection and PA
    • PA patients have a lower frequency of Hp positivity than the general population
  • Atrophy endured from AIG may deter Hp colonization as even fewer PA patients with severe gastric body atrophy show evidence of infection (Pérez-Pérez, 1997; Presotto et al., 2003)
  • Study by Saenz et al.
    • In Hp-infected mice an atrophy-induced increase in gastric pH
      • Promotes Hp corpus colonization
      • Hp preferentially binds deeper within antralized metaplastic corpus glands (Sáenz et al., 2019)
  • This may make it more difficult to detect Hp in severely diseased, shallow human biopsy samples !!
  • Hp-infected individuals
    • Can have seroconversion
    • Or the loss of detectable serologic anti-Hp immunoglobulin after years of infection with and without successful eradication therapy (Valle et al., 1996; Perez-Perez et al., 2002; Veijola et al., 2007).
  • Severe gastritis
    • Leading to clearance or deep binding of bacteria
    • Combined with a loss of serologic positivity
    • Could explain why PA patients don’t show higher rates of Hp
      • Although these ideas still do not prove that AIG is triggered by infection
  • www.frontiersin.org/articles/10.3389/fcell.2021.752346/full

Hypochlorhydrie

  • Another outcome from the loss of acid-secreting parietal cells is hypochlorhydria.
  • Increased gastric pH
    • Enhances gastrin production from G cells in the stomach.
  • Gastrin acts on and induces hyperplasia of neuroendocrine ECL cells
    • Promote acid secretion from parietal cells (Walsh, 1990).
  • This type of hyperplasia is a common feature of AIG
    • Can lead to the development of generally benign neuroendocrine tumors (Müller et al., 1987; Coati et al., 2015).
  • www.frontiersin.org/articles/10.3389/fcell.2021.752346/full

Identifying food intolerances

  • Is the first step on the road to restoring gut health.
  • Hidden food intolerances or sensitivities create an inflammatory environment that contributes to dysbiosis, leaky gut, intestinal stress, immune system dysfunction...

2020 observational study, 58% of chronic atrophic gastritis patients

  • Reported that their symptoms correlated with dietary factors [18].
  • Foods associated with increased atrophic gastritis symptoms in observational studies and surveys include:
    • Alcohol
    • Spicy foods
    • Sugary foods
    • Fish
    • Legumes
    • Meat
    • Coarse cereals (sorghum, pearl millet, ragi, small millets, maize, and barley)
    • Dairy
  • Experimenting with temporary elimination of these foods and observing how your body responds, you will have a clearer picture
  • drruscio.com/autoimmune-atrophic-gastritis/

Genetická predispozice

  • Existuje určitá genetická predispozice pro autoimunitní perniciózní anémii, která může být dědičná.

Infekce

  • Některé infekce, jako je například Helicobacter pylori, mohou způsobit narušení tvorby vnitřního faktoru v těle a vést k autoimunitní perniciózní anémii.

Vliv prostředí

  • Některé chemikálie a znečištění prostředí mohou ovlivnit imunitní systém těla a vést k autoimunitní perniciózní anémii.

Nedostatečný příjem vitamínu B12 z potravy

  • Zvýšené riziko vzniku autoimunitní perniciózní anémie.
  • Toto se obvykle týká veganské a vegetariánské stravy, protože vitamín B12 se přirozeně vyskytuje především v živočišných produktech, jako jsou maso, vejce a mléčné výrobky.

Chirurgické zákroky

  • Některé chirurgické zákroky, jako je například gastrektomie, mohou způsobit narušení tvorby vnitřního faktoru v těle a vést k autoimunitní perniciózní anémii. (???)

Změny hormonální hladiny

  • Těhotenství a menopauza, mohou ovlivnit imunitní systém těla a vést k auto

Léky

  • Inhibitory protonové pumpy
  • Antacidní přípravky, mohou snižovat tvorbu kyseliny v žaludku, což může narušit tvorbu IF a vést k AP.

Poškození thymu

Neonatal infection with murine CMV and adult infection with Salmonella typhimurium

  • Result in thymic atrophy as well as decreased DP and CD4 SP thymocytes
  • Neither infection has been reported to result in autoimmunity (Majumdar et al., 2017; Price et al., 1993).

Trypanosoma cruzi, HIV, measles, lymphocytic choriomeningitis virus, and Zika virus

  • Can cause thymic involution
  • Altered thymic epithelia,
  • A clear link to development of autoimmunity independent of active pathogen replication has not been established (Autran et al., 1996; Elsaesser et al., 2020; Linhares-Lacerda et al., 2015; Messias et al., 2020; Valentin et al., 1999).

Attenuated yellow fever virus

Snížení počtu buněk thymu v dětství

MTV, aka murine herpesvirus 3 or mouse thymic lymphotropic virus

  • Viruses infect the thymus
  • Cause transient CD4 single-positive (SP) and double-positive (DP) thymocyte depletion
    • After neonatal infection (Morse and Valinsky, 1989; Patel et al., 2017)
  • MRV causes thymocyte depletion in mouse strains that were resistant to MTV (Cross et al., 1979; Patel and Yokoyama, 2017a; Rowe and Capps, 1961)
  • MRV is a natural murine pathogen, providing an opportunity to perform in vivo studies evaluating the impact of a viral infection on development of autoimmune disease.
  • rupress.org/jem/article/219/3/e20211403/213039/Disruption-of-thymic-central-tolerance-by

O úroveň výše

Poslední aktualizace: 27. 10. 2023 19:24:04