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Background: Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and its changes are believed to be a significant contributor to inflammaging. Gonadal hormones affect IgG glycome composition, suggesting that alterations in IgG glycosylation might be one of the molecular mechanisms behind increased disease risk in perimenopause. Methods: IgG was isolated from 5,354 plasma samples collected from 1,940 females and 113 males at multiple time points. IgG glycans were released, labelled with a fluorescent dye and analysed by ultra-high-performance liquid chromatography. Mixed modelling was used to determine average levels of individual IgG glycans in pre-menopausal women, menopausal women, and men. Findings: Large and statistically significant differences in IgG glycome composition were observed, mainly reflecting decreased galactosylation and sialylation of glycans in menopausal women. During perimenopause women had a significant higher rate of increase in agalactosylated structures (0.051/yr; 95%CI = 0.043 - 0.059, p

Background Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease. Methods Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery. Results We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients' plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP. Conclusions Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation. General significance To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.

Background: Although endoscopy is the gold standard for the assessment of activity in Crohn's disease (CD), it should be integrated with clinical, laboratory, and radiological data. In particular, it is still unclear when MRI should be performed. Aim: To evaluate the advantages and limitations of endoscopy and MRI to assess disease activity and severity in a series of CD patients. Material and methods: 50 consecutive patients with endoscopically provenCD underwentMRI enterography for the staging at diagnosis or follow-up. Endoscopic activity was measured by SES-CD (range 0-40) with active mild,moderate ad severe disease defined as a scores 4-10,11-19 and >20 respectively. MRI activity was measured by a validated quantitative score which integrates both mural and extramural involvement (Magnetic Resonance Enterography global score,MEGS,range 0-296), with active disease present for a ≥ 1 score. CDAI, CRP and fecal calprotectin (FC) were measured in all participants (positivity cut-off respectively >0,50 mg/dl and >150 μg/gr). Results: We enrolled 20 males and 30 females (diagnosis in 62%, follow-up in 38%), mean age 38±15 years,mean disease duration 5,4±5 years. SES-CD and MEGS were well correlated (r=0,42, p=0.001); both SESCD andMEGS show correlation with clinical (CDAI r=0,51,r=0,59, p