Glycosylation of plasma IgG in colorectal cancer prognosis

In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glycan structures were strongly associated with all-cause (q < 0.01) and CRC mortality (q = 0.04 for galactosylation and sialylation). Clinical algorithms showed good prediction of all-cause and CRC mortality (Harrell’s C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). The inclusion of IgG glycan data did not lead to any statistically significant improvements overall, but it improved the prediction over clinical models for stage 4 patients with the shortest follow-up time until death, with the median gain in the test AUC of 0.08. These glycan differences are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. In the absence of validated biomarkers to improve upon prognostic information from existing clinicopathological factors, the potential of these novel IgG glycan biomarkers merits further investigation

Subclass-specific IgG glycosylation is associated with markers of inflammation and metabolic health

Abstract This study indicates that glycosylation of immunoglobulin G, the most abundant antibody in human blood, may convey useful information with regard to inflammation and metabolic health. IgG occurs in the form of different subclasses, of which the effector functions show significant variation. Our method provides subclass-specific IgG glycosylation profiling, while previous large-scale studies neglected to measure IgG2-specific glycosylation. We analysed the plasma Fc glycosylation profiles of IgG1, IgG2 and IgG4 in a cohort of 1826 individuals by liquid chromatography-mass spectrometry. For all subclasses, a low level of galactosylation and sialylation and a high degree of core fucosylation associated with poor metabolic health, i.e. increased inflammation as assessed by C-reactive protein, low serum high-density lipoprotein cholesterol and high triglycerides, which are all known to indicate increased risk of cardiovascular disease. IgG2 consistently showed weaker associations of its galactosylation and sialylation with the metabolic markers, compared to IgG1 and IgG4, while the direction of the associations were overall similar for the different IgG subclasses. These findings demonstrate the potential of IgG glycosylation as a biomarker for inflammation and metabolic health, and further research is required to determine the additive value of IgG glycosylation on top of biomarkers which are currently used

Exercise induce hemoconcentration following spleen contraction in subjects with COPD

The blood-boosting spleen contraction represents a potential protective response to hypoxia by raising the blood gas storage capacity. Human spleen contraction has been observed during exercise, apnea and simulated altitude resulting in ejection of stored red blood cells into circulation. High-altitude exposure has been shown to increase spleen contraction suggesting that long-term hypoxia may improve the response in humans. Subjects with COPD are often exposed to hypoxia, which limits their physical performance. However, it is not known if spleen contraction occurs in subjects with COPD. Our aim was to reveal whether subjects with COPD recruit the spleen erythrocyte reserve during mild exercise. Methods SpO2, spleen volume and Hb were measured before and after 6 min walking test (6MWT) in 24 subjects with COPD. Results were analyzed for all subjects pooled and for subject groups with resting SpO2 above and below 90 % separated and expressed as mean. Results 6MWT reduced SpO2 from 91 to 83 % and spleen volume from 254 to 181 mL, while Hb increased from 150 to 154 g/L (p = 0.001 for all). Compared to subjects with SpO2 &gt; 90 %, the group with SpO2 &lt; 90 % displayed the largest resting spleen volume (339 vs 202 mL; p = 0.001) and the most pronounced spleen volume reduction (139 vs 40 mL; p = 0.007). Conclusion Exercise with hypoxia evokes spleen contraction in subjects with COPD and may represent a protective response during periods of hypoxia. The larger spleen volume and more pronounced contraction in the most hypoxic subjects may suggest long-term adaptation to hypoxia