F2 og F2R

Komplement og koagulations kaskaden bliver aktiveret ved et inflammatorisk respons. Dette afspejles i proteom studiet af cerebrospinalvæske fra ME patienter. Thrombin er en del af dette respons. Studiet viste, at fragment af prothrombin precusor (F2) var forhøjet. Værdi for ME patienter: 126, normal værdi: 27. (1)

Genet for koagulations faktor II trombin receptor (F2R) er fundet hypomethyleret hos ME patienter. Det er gen nr. 9 på listen over epigenetisk ændrede gener, der relaterer til ME patienters livskvalitet (2).

Alfa-2-macroglobulin (se sidste blogindlæg) fungerer inhibitorisk i koagulationsprocessen.

Er der noget her der hænger sammen?

Referencer:

1. Schutzer et al: Distinct Cerebrospinal Fluid Proteomes Differentiate Post- Treatment Lyme Disease from Chronic Fatigue Syndrome. PLOS One February 2011, volume 6, Issue
2. Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11

alfa-2-macroglobulin og anti-sense RNA

de Vega et al fandt 12.608 forskelligt methylerede steder i generne hos ME patienter i forhold til raske kontrolpersoner. Da disse ændringer blev relateret til ME patienternes livskvalitet kom genet for alfa-2-macroglobulin anti-sense RNA 1 ud som nr. 5-hypermethyleret (tabel S7 i ref 1).

Anti-sense RNA er komplementær til mRNA med det formål at inhibere translationen af mRNA. Dvs hvis et anti-sense gen bliver nedreguleret ved en hypermethylering, så er der ikke noget til at inhibere translationen af mRNA. Så resultatet må formodes at være rigelige mæmgder af alfa-2-macroglobulin.

To uafhægige proteomstudier på spinalvæske fra ME patienter har påvist opregulerede niveauer af alfa-2-macroglobulin (2,3).

Referencer:

1. Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11
2. Schutzer et al: Distinct Cerebrospinal Fluid Proteomes Differentiate Post- Treatment Lyme Disease from Chronic Fatigue Syndrome. PLOS One February 2011, volume 6, Issue
3. Baraniuk et al: CFS-related proteome in human CSF. BMC Neurology 2005, 5, 22.

Liver metabolism, GRAMD1A and ME

Germain et al found disturbances in fatty acid and lipid metablism in ME patients. The results were suggestive to damage to liver / a deficiency in liver activity (1).

de Vega et al showed that the most hypermethylated gene associated with quality of life in ME patients was GRAMD1A. A hypermethylated gene is often associated with supressed transcription (2).

GRAMD1A promotes the expansion of hepatocellular carcinoma stem cell and hepatocellular carcinoma growth through STAT5 (3).

If up-regulated GRAMD1A up-regulates STAT5 and induces growth in cancer cells, what do a down-regulated GRAMD1A do in ME patients? In liver cells? In lymphocytes?

STAT5 is involved in lymphocyte development and transformation. And STAT5 promotes the proliferation, survival and selfrenewal of hematopoietic stem cells (ref 21-24 in ref 3).

References:

1. Germain et al: Metabolic profiling of a ME/CFS discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol. BioSyst. 2017, 13, 371
2. Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11
3. Binsheng Fu et al: GRAMD1A promotes the expansion of hepatocellular carcinoma stem cell and hepatocellular carcinoma growth through STAT5. Nature Scientific Reports, 2. sept 2016.