hs-CRP vs IgG Glycans: A More Reliable Way to Measure Systemic Inflammation

Every hs-CRP result carries noise. A single elevated reading might reflect a genuine inflammatory disease, a mild cold from the week before, or nothing clinically meaningful at all. hs-CRP is the most widely ordered inflammation marker in practice, and it earns that position for acute illness. But chronic, low-grade inflammation, the kind driving cardiovascular disease, autoimmune conditions, and biological aging, behaves differently from the spikes hs-CRP was built to catch, which is why a longer half-life marker like IgG glycans becomes useful. To see why, it helps to start with what hs-CRP actually measures, and where that mechanism starts to break down.

For the fuller picture of why chronic inflammation drives biological aging, read Chronic Inflammation & Inflammaging: The Hidden Driver of How You Age. 

How hs-CRP responds to inflammation

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to inflammation. When the body is injured or fighting an infection, it triggers what's called the acute-phase response. Immune cells release signaling molecules called cytokines, which stimulate the liver to produce CRP and other acute-phase proteins that get released into the bloodstream to help tackle the problem.

"Inflammation is a process for how you eliminate a threat in an organism. If bacteria comes through a cut in your skin, and it's growing and feeding on you, you send your immune system to kill it. This is when inflammation is good. You have to kill the bacteria, then heal the wound, and then you're fine again."

— Prof. Gordan Lauc, Co-Founder and Chief Scientific Officer, GlycanAge; Professor of Biochemistry and Molecular Biology, University of Zagreb

The function of CRP can be divided into 2 steps:

• Recognition and binding of molecules present on the surface of pathogens

• Activation of various immune responses that help clear out the pathogens

CRP can activate multiple immune pathways:

• The complement pathway - a series of biochemical reactions that enhance the immune system's ability to eliminate pathogens and damaged cells

• Phagocytosis - a process in which immune cells engulf and digest pathogens or cellular debris

• CRP can also bind directly to phosphocholine, a molecule found in bacterial cell walls, and act as an opsonin, marking pathogens for destruction by immune cells

What else raises hs-CRP

This responsiveness is exactly what makes hs-CRP useful for detecting acute illness, and exactly what makes it noisy as a chronic-disease marker. The same rise in CRP can be triggered by very different underlying causes, from a minor infection to a major autoimmune flare, which makes a single reading difficult to interpret in isolation without additional context.

Acute infections

Both bacterial and viral infections can cause elevated CRP levels, with bacterial infections typically causing a much greater increase, sometimes up to 1000 fold. This increase happens quickly, often before symptoms appear, which makes hs-CRP a good marker for early infection but a poor one for distinguishing infection from other causes of inflammation.

Chronic inflammatory diseases

Autoimmune diseases are marked by chronic, low-grade inflammation rather than the sharp spikes seen in acute infection, so the rise in CRP is far less pronounced. This same low-grade elevation shows up in rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease, alongside dozens of unrelated conditions, which is part of why hs-CRP alone cannot pinpoint a cause.

Cardiovascular disease

Elevated CRP is strongly associated with increased risk of cardiovascular events, including heart attack and stroke. Because CVD, like autoimmune disease, involves low-grade chronic inflammation, standard CRP tests (which cannot measure below 3 mg/L) miss it entirely, which is why hs-CRP, sensitive to levels as low as 0.1 mg/L, is used for CVD risk assessment instead. Even then, hs-CRP is only useful when combined with other markers such as cholesterol and blood pressure, since relying on it alone is not sufficient for proper risk assessment.

Why hs-CRP fluctuates and IgG glycans don't

The core issue is half-life. hs-CRP has a half-life of less than one day, so it reflects whatever is happening in the body at that specific moment, a snapshot of current stress. IgG glycans, the molecules GlycanAge measures, are attached to antibodies with a half-life of 2 to 3 weeks, so they behave more like a film of biological aging built up over time than a single frame. That difference means the two markers answer different clinical questions, and neither one fully replaces the other.

"We cannot use something as a biomarker unless we can measure it, and it has to be measured reproducibly. If I measure it in this person, I want to know that if I measure it again in the same lab, I'll get the same result, as long as nothing else has changed."

— Prof. Samia Mora, MD, MHS, Associate Professor of Medicine, Harvard Medical School; Division of Preventive Medicine, Brigham and Women's Hospital 

That difference in half-life is also a difference in what each marker can tell a practitioner:

Because hs-CRP resets so quickly, a practitioner needs multiple measurements to establish a reliable average for any patient with fluctuating exposures, which is most patients. IgG glycans are less prone to that kind of noise from transient lifestyle factors, which makes a single result more informative for tracking chronic inflammatory load without needing to average out day-to-day swings.

CRP testing and interpretation

CRP tests are blood tests for inflammation routinely used in medical practice for assessing acute inflammation characteristic of infections, but also for detecting autoimmune conditions and assessing CVD risk. Standard CRP tests detect levels above 3 mg/L and are used for acute inflammatory responses, while high-sensitivity CRP (hsCRP) tests detect concentrations as low as 0.1 mg/L and are used for CVD and autoimmune risk assessment. 

When should this test be ordered?

CRP testing is recommended when a patient is suspected of having an infection, even before symptoms appear, and hsCRP testing is used in assessing autoimmune conditions and cardiovascular risk. The limitation is that CRP tests can't identify the source of inflammation, only its presence. If a patient is on treatment to reduce inflammation, CRP tests can help track whether that treatment is working, though repeat testing is needed to separate signal from noise.

Understanding results

Normal CRP levels in healthy individuals are typically below 3 mg/L. Unhealthy lifestyle habits or underlying autoimmune or cardiovascular disease may cause a slight elevation, up to around 10 mg/L. Levels above this range may indicate an acute infection, and levels exceeding 50 mg/L are more indicative of acute bacterial infection specifically.

Non-disease causes of a high hs-CRP

Beyond active disease, CRP shifts with everyday factors that have nothing to do with a diagnosis. Diet, physical activity, sleep quality, and stress levels can all move the number, quietly and without any acute trigger. These effects build slowly, so they rarely explain a single result but they do add background noise to every reading taken over time.

Genetics adds another layer. Specific genetic variants can raise a person's baseline CRP even when they're healthy, and genetic differences can determine whether something like smoking raises one patient's CRP while leaving another's unchanged. Medications compound this further, since statins, for example, lower CRP independently of their effect on cholesterol. That's clinically useful, but it also means a change in CRP doesn't always mean a change in underlying inflammation. Each of these factors is a source of variability that a single hs-CRP reading cannot separate out on its own.

CRP’s role in predicting future health issues

hs-CRP has shown genuine prognostic potential for future cardiovascular events, but its use in risk assessment remains limited on its own. It's advised to combine it with additional CVD risk markers rather than rely on it in isolation. That advice exists precisely because hs-CRP's volatility limits its standalone predictive power for chronic, age-related disease.

CRP levels can often be lowered through a better diet, regular exercise, reduced smoking and alcohol use, and stress management, though for autoimmune disease and CVD, lifestyle change alone often isn't enough and medication is needed to resolve the underlying inflammation.

Why IgG glycans complement hs-CRP testing in practice

hs-CRP and IgG glycans aren't measuring the same thing, and that's the point. hs-CRP captures a patient's acute inflammatory status. GlycanAge, by analyzing glycans (complex carbohydrates attached to antibodies that regulate the inflammatory status of the immune system), captures the chronic, cumulative inflammatory load driving biological aging.

"The changes in IgG glycosylation start way before the person actually starts to feel that something is wrong."

— Dr. Olga Zaytseva, PhD, Geneticist and Researcher, Genos Glycoscience Research Laboratory, Zagreb

Considering chronic inflammation is one of the main drivers of disease, this distinction matters in practice. GlycanAge can help reveal potential health risks earlier (originally "help you detect potential health risks") than a single hs-CRP reading would, and it is still responsive enough to show changes in inflammation following an intervention, whether lifestyle-based or medical, without the noise of day-to-day fluctuation.

Used together, hs-CRP flags acute events while GlycanAge tracks the chronic trend beneath them, giving practitioners a fuller picture of a patient's inflammatory status than either marker alone.

Explore how GlycanAge fits into clinical practice or view a sample provider report.

External sources

• https://pmc.ncbi.nlm.nih.gov/articles/PMC161431/ — Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003 Jun;111(12):1805-12. 

• https://www.ncbi.nlm.nih.gov/books/NBK441843/ — Singh B, Goyal A, Patel BC. C-Reactive Protein: Clinical Relevance and Interpretation. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 May.

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375626/ — Lopez-Roblero A, et al. Single-nucleotide polymorphisms in the promoter of the gene encoding for C-reactive protein associated with acute coronary syndrome. Biomed Rep. 2024 Nov;21(5):150.

• https://pmc.ncbi.nlm.nih.gov/articles/PMC6204840/ — Booth BJ, Ramakrishnan B, Narayan K, Wollacott AM, Babcock GJ, Shriver Z, Viswanathan K. Extending human IgG half-life using structure-guided design. MAbs. 2018 Oct;10(7):1098-1110.

• https://pmc.ncbi.nlm.nih.gov/articles/PMC4049143/ — Krištić J, Vučković F, Menni C, et al. Glycans are a novel biomarker of chronological and biological ages. J Gerontol A Biol Sci Med Sci. 2014 Jul;69(7):779-89.

• https://www.nature.com/articles/s41574-018-0059-4 — Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018 Oct;14(10):576-590.