Publications and news

The importance of IgG glycosylation—What did we learn after analysing over 100,000 individuals

Jasminka Krištić, a Genos team member, and Gordan Lauc, one of the principal investigators of the GlycanSwitch project, recently published an in-depth review on the importance of immunoglobulin G (IgG) glycosylation in the journal Immunological Reviews.

This comprehensive review, exceeding 15,000 words and accompanied by informative figures, covers various aspects of IgG glycosylation, including the structures of glycans found on IgG, how glycosylation affects IgG effector functions, and key findings from analysing over 100,000 IgG glycomes derived from the general population, disease-specific, and intervention studies.

Among many topics, the review also discusses the characteristics and roles of Fab glycans and highlights IgG glycosylation's relevance in autoimmune diseases, including rheumatoid arthritis — a central focus of the GlycanSwitch project.

#CollaborativeResearch #ERCConsortium

For more details, the full article can be accessed here.

Glycan clock of ageing-analytical precision and time-dependent inter- and intra-individual variability

Borna Rapčan, from Genos, has advanced the understanding of ageing biomarkers by shedding light on different types of analytical precision and time-dependent inter- and intra-individual variability of human immunoglobulin G (IgG) N-glycome.

Using 312 plasma samples analysed in tetraplicates over 26 days, the study demonstrated consistently low coefficients of variation for intermediate precision across all test samples. These results highlight the reliability of the CGE-LIF methodology for N-glycan analysis, ensuring precise measurements critical for studying glycosylation changes associated with ageing and different (patho)physiological conditions.

In addition to precision, this work provides valuable insights into the time-dependent inter- and intra-individual variability of IgG glycosylation patterns. By examining short-term variability in two cohorts and long-term stability in two individuals monitored for up to a decade, the study uncovered significant findings. Short-term follow-up highlighted the stability of the IgG glycome, with potential influences of hormonal cycles on glycan composition in women. Long-term monitoring identified persistent trends in specific glycan traits linked to ageing while also showing responses to changes and life events such as biological age reduction interventions and acute diseases. These findings demonstrate how glycosylation patterns can adapt to environmental and physiological factors while maintaining their relevance as biomarkers for tracking age-related health changes.

These contributions provide a deeper understanding of IgG glycome dynamics, advancing its potential applications in precision diagnostics and personalized medicine for age-related health concerns.

#CollaborativeResearch #ERCConsortium #AnalyticalPrecision #GlycomeVariability

For more details, the full article can be accessed here.

Anti-TNF biologicals enhance the anti-Inflammatory properties of IgG N-Glycome in Crohn’s Disease

A study led by Genos team member Maja Hanić and colleagues significantly expanded our understanding of the impact of monoclonal antibodies on immunoglobulin G (IgG) glycosylation in patients suffering from Crohn's disease (CD). Using a well-established and robust UHPLC method for glycan analysis in a high-throughput manner, the longitudinal effects of the anti-TNF drugs infliximab and adalimumab on IgG glycosylation were assessed. Significant changes in IgG glycosylation were observed, indicating decreased systemic inflammation. Furthermore, the predictive potential of the IgG N-glycome in determining therapy response to anti-TNF treatment was evaluated, paving the way for further research in the field of personalized medicine.

The insights gained through this collaboration are anticipated to benefit the GlycanSwitch consortium by improving the understanding of the intricate relationship between anti-TNF drugs and IgG N-glycosylation in the management of Crohn's disease.

#CollaborativeResearch #ERCConsortium #biologics #glycomics

For more details, the full article can be accessed here.

High-throughput N-glycan analysis in aging and inflammaging: State of the art and future directions

Ana Cindrić and the team at Genos have made strides in understanding the links between aging, inflammation, and glycan profiles. Their review focuses on advanced techniques for high-throughput N-glycan analysis and their utilization for the detailed exploration of glycans’ roles in aging and inflammaging.

This research is positioned to enhance our understanding of aging-related diseases, paving the way towards unveiling novel biomarkers and therapeutic targets. By providing insights into how chronic inflammation and glycosylation changes interplay with disease, this work supports a holistic view of aging at the molecular level.

The research team aims to further investigate inflammaging, as well as support and motivate collaborations on the topic, which could transform therapeutic strategies for age-related diseases.

#CollaborativeResearch #ERCConsortium #Glycomics #Aging #Inflammaging

For more details, the full article can be accessed here (and here).

Mapping of the gene network that regulates glycan clock of ageing

A genome-wide association study (GWAS) led by Genos team member Azra Frkatović-Hodžić and colleagues has revealed insights into the genetic regulation of immunoglobulin G (IgG) galactosylation process.

We have identified novel genome-wide loci associated with IgG galactosylation, a feature known to closely correlate with aging. Functional analyses further demonstrated that some of these genes influence the IgG glycome profile in vitro.

Additionally, we have found that genetic loci associated with IgG galactosylation colocalize with risk loci for diseases such as systemic lupus erythematosus, schizophrenia, breast cancer, and COVID-19.

This study lays the foundation for further investigations into the genetic regulation of IgG glycosylation within the scope of the GlycanSwitch project. The identified genes not only provide a basis for follow-up functional studies but also support the validity of using in vitro systems to test GWAS hits related to IgG glycosylation.

#CollaborativeResearch #ERCConsortium #InnovativeMethodology

For more details, the full article can be accessed here.

Long-term culturing of FreeStyle 293-F cells affects immunoglobulin G glycome composition

Genos' team has made a significant contribution to our understanding of changes in immunoglobulin G (IgG) glycosylation associated with cardiovascular disease

In collaboration with leading researchers in the area of cardiovascular diseases, we have explored a predictive potential of IgG glycosylation for cardiovascular events by analyzing samples from two case-control cohorts. This study has shown that agalactosylated IgG glycan is associated with an increased risk of CVD and several digalactosylated and sialylated IgG glycans are associated with decreased risk of CVD. We have calculated the IgG glycan score that positively associates with future cardiovascular diseases making significant progress in the identification of glycan-based biomarkers. Glycans are the result of genetic, epigenetic, and environmental factors making them more amenable to intervention, compared to biomarkers based on other biological molecules.

These results shed light on the potential role of IgG glycosylation in cardiovascular disease risk through regulation of pro- or anti-inflammatory responses of IgG warranting future studies on the role of glycosylation in cardiovascular disease development and progression, as well as the role of glycans as potential drug targets.

#CollaborativeResearch #ERCConsortium #Glycomics #Immunoglobulins

For more details, the full article can be accessed here.

A robust nanoscale RP HPLC-MS approach for sensitive Fc proteoform profiling of IgG allotypes

Constantin, a team member of the Center for proteomics and Metbolomics at the Leiden University Medical Center, has made a significant leap in glycoimmunology with a novel nanoscale RP HPLC-MS methodology.

This state-of-the-art technique revolutionizes our ability to analyze Fc proteoforms of IgG allotypes with unprecedented sensitivity and specificity.

As we move forward, this method is set to be a cornerstone in the research efforts of the GlycanSwitch consortium.

This consortium, benefiting from the combined expertise of the CPM and Rheumatology departments, aims to delve deeper into the complexities of the ACPA response in different biological fluids like plasma and synovial fluids.

The insights gained through this collaboration are expected to open new pathways in understanding this painful autoimmune disease.

We are on the cusp of a new era in glycoimmunology research, and the contributions of Constantin's methodology are paving the way for transformative discoveries.

#CollaborativeResearch #ERCConsortium #innovativeMethodology

For more details, the full article can be accessed here.

N-linked Fc glycosylation is not required for IgG-B-cell receptor function in a GC-derived B-cell line

Our latest study of Theresa Kissel and co-authors, focusing on the fascinating world of B cells has unveiled groundbreaking insights that are reshaping our understanding of Fc glycosylation and its role in antibody functionality.

Key findings:

The glycosylation of the gamma heavy chain in B-cell receptors, contrary to prior beliefs, is not crucial for their expression or function.
This revelation indicates that B-cells can activate and produce antibodies effectively, even in the absence of Fc glycans.
This research is a pivotal step forward in immunology, opening new doors to understanding B-cell biology.

As we move forward, this method is set to be a cornerstone in the research efforts of the GlycanSwitch consortium.

The insights gained through this collaboration are expected to open new pathways in understanding this painful autoimmune disease.

We are on the cusp of a new era in glycoimmunology research, and the contributions of Constantin's methodology are paving the way for transformative discoveries.

#CollaborativeResearch #ERCConsortium #innovativeMethodology

For more details, the full article can be accessed here.