Genomics in MEA gene variant of iNOS has been identified as a risk locus in ME (2):
Proteomics in METhe pathway "Production of NO and ROS in macrophages" was upregulated in the cerebrospinal fluid from ME patients (table S6 in ref 3).
Transcriptomics in MEFunctional Network Analysys of gene transcripts from ME immune cells showed thar the pathway "Production of NO and ROS in macrophages" was enriched (p-value = 0,000018) (4).
Macrophages and the ME-IDO-metabolic trapThe ME-IDO metabolic trap hypothesis tell us that the kynurenic pathway may be blocked in dendritic cells and macrophages. This means decreased metabolites from the pathway (5).
During inflammation and resolution of inflammation, this may be going on in normal cells (6) :
- Increased IDO activity
- Increased kynurenic acid (KYNA) production
- Increased GPR35 activation (KYNA activates GPR35)
- Decreased iNOS expression
Figure 2 from ref 6 Wirthgen et al (2018).
Is this what is going on in ME macrophages???:
- Decreased IDO activity
- Decreased KYNA production
- Decreased GPR35 activation
- Increased iNOS expression
References:1) iNOS signaling: https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=252
2) Whole Genome Sequencing and Analysis of ME/CFS https://www.youtube.com/watch?v=nIJX-Q7w_Z4
3) Schutzer et al: Distinct Cerebrospinal Fluid Proteomes Differentiate Post- Treatment Lyme Disease from Chronic Fatigue Syndrome. PLOS One February 2011, volume 6, Issuehttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017287
4) Sweetman et al: Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome. Sweetman et al: Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738418820402. doi: 10.1177/2058738418820402.
Metabolic Traps in ME/CFS - Research Update by Dr. Robert Phair
6) Wirthgen E Hoeflich A, Rebl A, Günther J.: Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions
Front Immunol. 2018 Jan 10;8:1957. doi: 10.3389/fimmu.2017.01957. eCollection 2017.
Send en kommentar
Bemærk! Kun medlemmer af denne blog kan sende kommentarer.