Inflammation is the body’s response to tissue damage. The inflammatory process has drastic effects on metabolism and causes stress to the body. In the last few years, new tests for acute inflammation have entered the veterinary market. However, tests for chronic, low-grade inflammation are still lacking. The detection of low-grade inflammation is important, since while symptoms can be very mild, the inflammation still causes stress on the body and predisposes to more severe inflammatory diseases. There are three inflammatory markers included in PetMETA. GlycA is a very interesting, new inflammatory marker, that has been associated with low-grade inflammation and all-cause mortality in humans.

 

GlycA detects chronic, low-grade inflammation

GlycA is a novel inflammatory marker, that combines the N-acetyl group signals of several acute phase glycoproteins and glycosylated lipoproteins. The molecules contributing to the GlycA signal are alpha-1-acid glycoprotein, alpha-1-antitrypsin, haptoglobin, transferrin, alpha-1-antichymotrypsin, and glycosylated lipoproteins. GlycA rises in inflammatory conditions both due to an increase in the concentration of acute phase glycoproteins and because of changes in their acetylation. The greatest acute phase protein contributor to the GlycA signal is alpha-1-acid glycoprotein. High triglyceride levels can also increase GlycA levels, which is why GlycA levels should always be evaluated against triglyceride levels.
In human medicine, GlycA-levels have been associated with chronic low-grade inflammation, risk of severe infection, all-cause mortality, diabetes, cardiovascular disease and several chronic inflammatory diseases. Changes in GlycA-concentrations in various diseases have not yet been published in dogs, but the concentration of the greatest contributor to the GlycA-signal, alpha-1-acid glycoprotein, is known to rise in many inflammatory diseases, such as parvoviral enteritis, canine distemper, pyometra, pancreatitis, renal insufficiency, cancer and IMHA.

Albumin is a commonly used inflammatory marker

Albumin is the most abundant protein in serum. Albumin is a routinely used biomarker for hepatic and renal diseases, fluid balance and inflammatory diseases, and is included in most clinical chemistry profiles. Albumin is a so-called negative acute phase protein, since its concentration falls in inflammatory conditions. This fall is mediated by declined formation of albumin, increased albumin degradation and leakage of albumin into the extravascular space. In chronic inflammatory diseases, malnutrition also plays a part in lowering the albumin concentration, since adequate protein intake is necessary for albumin synthesis. Albumin concentration of 20-25g/l is considered mild hypoalbuminemia, 15-20 as moderate hypoalbuminemia and below 15g/l as severe hypoalbuminemia. Severe hypoalbuminemia causes water to leak out of the blood vessels, causing edema/ascites.

HDL-cholesterol has many functions

In humans, low cholesterol, especially low HDL cholesterol, has been found to be associated with inflammation. The anti-inflammatory effect of HDL particles is believed to be caused by their ability to clear bacterial toxins, to prevent release of cytokines, and by transporting cholesterol to the adrenal glands for steroid synthesis. In dogs, low HDL cholesterol has been associated with parvoviral enteritis, leishmaniasis and babesiosis, and its usefulness as a canine negative inflammatory marker is under investigation. In humans, it has been found that not only the concentration of HDL-cholesterol changes, but also the composition and function of HDL-particles changes during inflammatory processes. During inflammation, esterified cholesterol decreases and triglycerides increase within HDL-particles and HDL-particles become oxidized. In dogs, changes in the structure and function of HDL particles during inflammatory conditions have not yet been investigated.

 

Additional information

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Gruppen, E. G. et al. GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality: results from the PREVEND study and meta-analysis. J. Intern. Med. (2019). doi:10.1111/joim.12953
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