HPLC Analysis of N-Glycans as Psoriasis Markers

One ongoing challenge in managing psoriasis is the lack of reliable biological markers that can accurately reflect how severe it is or how well a patient is responding to treatment. A recent research study focused on a group of molecules called glycans, sugar-based structures that attach to proteins and fats in the body and play important roles in a wide range of biological processes. When glycan patterns are disrupted, it has been linked to inflammatory conditions and certain cancers, making them an area of growing interest as potential markers of disease and targets for treatment. The researchers set out to explore whether specific glycan patterns in the blood could serve as useful indicators of psoriasis, specifically examined the ratio of two specific glycan types (one that carries a sugar called sialic acid and one that carries a different modification called fucose), referred to as the S/FA ratio. Blood samples from 45 psoriasis patients, 12 patients with a related skin condition called atopic dermatitis, and 19 healthy individuals were analyzed using high-performance liquid chromatography (HPLC). Their findings were published in the Journal of Dermatology.¹

Why Might N-glycans Be a Promising Solution to the Challenge of Finding Reliable Biomarkers for Psoriasis?

Psoriasis is a long-term condition in which the immune system drives inflammation, affecting both the skin and, in some cases, the joints. It is usually diagnosed by a doctor based on the appearance of the skin, with a tissue sample taken for closer examination when needed. While this approach works well in most cases, early, mild, or unusual presentations can be harder to identify with confidence. When it comes to tracking how severe the disease is or how well a patient is responding to treatment, doctors currently rely primarily on visual clinical assessment. Although newer targeted therapies and biologics have significantly improved outcomes for patients with severe or hard-to-treat psoriasis, finding reliable biological markers that can objectively measure disease severity and treatment response has proven to be a persistent challenge.^1,2

N-glycans are chains of sugar molecules that attach to proteins in the body, where they play important roles in helping proteins fold correctly, remain stable, and be released into the bloodstream. When they attach to a key immune protein called immunoglobulin G (IgG), they help regulate how the immune system responds, acting as a bridge between its two main defense mechanisms. Disruptions in these sugar-chain patterns on IgG have been linked to a range of conditions, including autoimmune diseases, infections, and cancer, and may offer clues about both diagnosis and disease outlook. From a practical standpoint, N-glycans are well suited for use as biological markers: they remain stable in blood over long periods, can be extracted and measured with relative ease, and can be tested using a routine blood draw. making them a low-burden option for patients and researchers alike.^1,3,4

Could the S/FA Ratio Serve as a Reliable Biomarker for Diagnosing Psoriasis and Monitoring Treatment Response?

The researchers compared the S/FA ratio against two existing markers already used in psoriasis research, CRP (a general marker of inflammation) and CCL20 (a protein linked to immune activity), and looked at how well it tracked with disease severity and response to treatment. The S/FA ratio was significantly higher in psoriasis patients than in healthy individuals and showed a meaningful correlation with a standard measure of disease severity that considers both the extent and intensity of skin involvement. In terms of diagnostic accuracy, the S/FA ratio performed comparably to both CRP and CCL20, correctly identifying psoriasis patients roughly 74% of the time.¹

Importantly, changes in the S/FA ratio tracked with improvements in disease severity following systemic treatment, including in patients receiving a newer class of targeted therapies that block a protein called IL-23. This suggests the ratio may be useful not just for diagnosis, but also for monitoring how well a treatment is working.¹

The S/FA ratio was not meaningfully affected by factors such as age, sex, other health conditions, or joint pain. It also did not differ significantly between psoriasis patients and those with atopic dermatitis, nor was it notably elevated in atopic dermatitis compared to healthy controls, which suggests some degree of specificity to psoriasis.¹

“The serum S/FA ratio,” wrote the authors of the paper,¹ “may serve as a glycan-based biomarker associated with disease severity and treatment response in psoriasis, although its ability to distinguish psoriasis from other inflammatory diseases requires further validation in larger and treatment-naïve cohorts.”

While they find these findings are promising, the researchers acknowledge that more work is needed. Larger studies that follow patients over time (ideally before they begin any treatment) will be necessary to confirm these results and to better understand how and when glycan patterns change in relation to the progression of psoriasis and its response to treatment.¹

References

1. Nishimura, K.; Oyama, N.; Hasegawa, T. et al. A Serum N-Glycan Ratio Associated With Disease Severity and Treatment Response in Psoriasis. J Dermatol. 2026. DOI: 10.1111/1346-8138.70316
2. Griffiths, C. E. M.; Armstrong, A. W.; Gudjonsson, J. E. et al. Psoriasis. Lancet 2021, 397 (10281), 1301-1315. DOI: 10.1016/S0140-6736(20)32549-6
3. Gudelj, I.; Lauc, G.; Pezer, M. Immunoglobulin G glycosylation in Aging and Diseases. Cell Immunol. 2018, 333, 65-79. DOI: 10.1016/j.cellimm.2018.07.009
4. Krištić, J.; Lauc, G. The Importance of IgG Glycosylation-What Did We Learn after Analyzing over 100,000 Individuals. Immunol Rev. 2024, 328 (1), 143-170. DOI: 10.1111/imr.13407