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Human Plasma IgG N-Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary
Ze-Jian Zhang1,2, Hui-Fang Wang3, Tian-Yu Lian1,2
1Department of Cardiology (Z.-J.Z., T.-Y.L., Y.-P.Z., X.-Q.X., F.G., Y.-P.W., J.-Y.L., K.S., C.L., Z.-C.J.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Insights
Chronic thromboembolic pulmonary hypertension (CTEPH) involves inflammation, linked to altered IgG glycosylation. This study reveals a proinflammatory IgG glycome signature in CTEPH, potentially aiding diagnosis and treatment.
Area of Science:
- Immunology
- Glycomics
- Pulmonary Hypertension Research
Background:
- Chronic thromboembolic pulmonary hypertension (CTEPH) pathogenesis remains unclear, with inflammation implicated.
- Immunoglobulin G (IgG) N-glycans are key regulators of systemic inflammation.
- Little is known about IgG N-glycosylation patterns in CTEPH patients.
Purpose of the Study:
- To map the IgG N-glycome in CTEPH patients.
- To gain insights into CTEPH pathogenesis.
- To identify potential novel biomarkers and therapeutic targets.
Main Methods:
- Plasma IgG N-glycans were analyzed using MALDI-TOF mass spectrometry in discovery and validation cohorts.
- Correlations between IgG N-glycans, clinical parameters (NT-proBNP), and inflammatory cytokines were investigated.
- IgG N-glycan quantitative trait loci were identified to explore underlying genetic mechanisms.
Main Results:
- CTEPH patients exhibited decreased IgG galactosylation, indicating a proinflammatory phenotype.
- IgG galactosylation levels strongly correlated with NT-proBNP.
- Pro-/anti-inflammatory IgG N-glycans aligned with inflammatory markers and relevant gene loci.
Conclusions:
- This study presents the first comprehensive IgG N-glycome signature in CTEPH, highlighting a proinflammatory phenotype.
- Plasma IgG galactosylation may serve as a marker for inflammation in CTEPH, pending further validation.
- The findings enhance understanding of CTEPH inflammation through a glycomic perspective.
Background:
The pathological mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood, and inflammation has been reported to be one of its etiological factors. IgG regulates systemic inflammatory homeostasis, primarily through its N-glycans. Little is known about IgG N-glycosylation in CTEPH. We aimed to map the IgG N-glycome of CTEPH to provide new insights into its pathogenesis and discover novel markers and therapies.
Methods:
We characterized the plasma IgG N-glycome of patients with CTEPH in a discovery cohort and validated our results in an independent validation cohort using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Thereafter, we correlated IgG N-glycans with clinical parameters and circulating inflammatory cytokines in patients with CTEPH. Furthermore, we determined IgG N-glycan quantitative trait loci in CTEPH to reveal partial mechanisms underlying glycan changes.
Results:
Decreased IgG galactosylation representing a proinflammatory phenotype was found in CTEPH. The distribution of IgG galactosylation showed a strong association with NT-proBNP (N-terminal pro-B-type natriuretic peptide) in CTEPH. In line with the glycomic findings, IgG pro-/anti-inflammatory N-glycans correlated well with a series of inflammatory markers and gene loci that have been reported to be involved in the regulation of these glycans or inflammatory immune responses.
Conclusions:
This is the first study to reveal the full signature of the IgG N-glycome of a proinflammatory phenotype and the genes involved in its regulation in CTEPH. Plasma IgG galactosylation may be useful for evaluating the inflammatory state in patients with CTEPH; however, this requires further validation. This study improves our understanding of the mechanisms underlying CTEPH inflammation from the perspective of glycomics.
