Translational glycobiology: from bench to bedside.

The importance of sugars to protein function is real and is of significant clinical relevance. Technology advances enable large population studies to be carried out, shedding light on individual sugar variation and variations with time. Three-dimensional mass spectroscopy on solid pathological specimens is going to open up a whole new world of pathology visualisation. The door is now open to exploit carbohydrate recognition in new therapeutics by identifying novel biomarkers in cancer to aid diagnosis, and also providing therapeutic targets for treatment. Glycan age correlates with biological age. This means we can map the reversal of biological age with exercise and diet.

A double-blind, randomized, placebo-controlled study to explore the efficacy of a dietary plant-derived polysaccharide supplement in patients with rheumatoid arthritis.

OBJECTIVES: There is increased interest in the potential benefits of complementary therapies, of which dietary plant-derived polysaccharides (dPPs) are an important component. We examined the impact of oral ingestion of a pre-biotic dPP supplement active compound (AC) on serum glycosylation and clinical variables associated with inflammation and general health in patients with RA. METHODS: A double-blind, placebo-controlled, parallel-group clinical trial was used. Participants were randomly assigned to receive AC (n = 33) or placebo (n = 36) for 6 months. Serum protein N-glycosylation was determined by mass spectrometry. Patient outcomes were assessed by validated clinical trial health questionnaires. The primary clinical efficacy variable was DAS-28. RESULTS: The groups had comparable baseline clinical characteristics. AC was well tolerated with low drop-out rates. Supplementation resulted in a 12% significant drop in the levels of the agalactosylated (G0F) glycans [8.10 (0.89) to 7.16 (0.60); P = 0.03], but had no significant overall effect on patient outcomes. The placebo-treated group showed no change in G0F but exhibited a reduction in the levels of fully digalactosylated (G2) glycans (11%; P = 0.03). Although not clinically significant, DAS scores were, however, marginally lower in the placebo group [difference = 0.63 (0.23) s.e.; 95% CI 0.17, 1.10; P = 0.009], as were two of the secondary variables. CONCLUSIONS: Short-term dietary supplementation with AC resulted in a moderate, but significant, reduction in G0F levels, but did not result in any clinically significant improvement in disease activity when assessing the study group as a whole.

Prevalence of anxiety and depression in osteoarthritis: use of the Hospital Anxiety and Depression Scale as a screening tool.

The aims of this study are to ascertain the prevalence of anxiety and depressive disorders in an outpatient population with osteoarthritis (OA), examine the interrelationships between severity of OA, pain, disability, and depression, and evaluate the Hospital Anxiety and Depression Scale (HADS) as a screening tool for this population. Patients with lower limb OA were evaluated with the Short Form McGill Pain and Present Pain Index Questionnaires, and a visual analogue scale, WOMAC Osteoarthritis Index-section C, and the HADS. Participants underwent a structured clinical interview by a liaison psychiatrist (AB). X-rays of affected joints were rated for disease severity. Fifty-four patients (42 females; mean age 63.3) were investigated. The prevalence of clinically significant anxiety and/or depression was 40.7% (95% confidence interval (CI), 27.6-55.0%). HADS was a good predictor of anxiety and depression with a sensitivity and specificity of 88% (95%CI, 64% to 99%) and 81% (95%CI, 65% to 92%), respectively. Pain correlated with HADS anxiety and depression scores (e.g. Rank correlation coefficients (Kendall's tau-b) between total HADS scores and Pain VAS scores 0.29; p=0.003). Disability was greater in patients with depression and/or anxiety (e.g. total HADS score; Kendall's rank correlation coefficient tau-b=0.26, p=0.007) OA severity as determined by radiological score was not a good predictor for anxiety nor depression and only weakly associated with disability. Anxiety and depression are very common in OA patients. HADS anxiety was a better predictor of diagnosed anxiety than HADS depression was of diagnosed depression. HADS is a valid and reliable screening instrument for detecting mood disorder, but not a diagnostic tool or a substitute for asking about symptoms of depression. The interrelationship between mental health, pain and disability is strong. We should therefore adopt a multidisciplinary approach to the management of OA.

Glyco-biomarkers: potential determinants of cellular physiology and pathology.

Once dismissed as just the icing on the cake, sugar molecules are emerging as vital components in life's intricate machinery. Our understanding of their function within the context of the proteins and lipids to which they are attached has matured rapidly, and with it the far reaching clinical implications are becoming understood. Recent advances in high-throughput glycomic techniques, glyco biomarker profiling, glyco-bioinformatics and development of increasingly sophisticated glyco-arrays, combined with our increased understanding of the molecular details of glycosylation have facilitated the linkage between aberrant glycosylation and human diseases, and highlighted the possibility of using glyco-biomarkers as potential determinants of disease and its progression. The focus of this review is to give an insight into the biological significance of these glycomodifications, highlight some specific examples of glyco-biomarkers in relation to autoimmunity and in particular rheumatoid arthritis, and to explore the exciting possibility of exploiting these for diagnostic and prognostic strategies.

The pivotal nature of sugars in normal physiology and disease.

Glycopathology has become the focus of considerable research in recent years as the role of glycosylation in the development, regulation, and progression of disease has come under increased scrutiny. Cracking the 'sugar-code' in biological systems that relate to both health and disease holds tremendous promise for deciphering disease mechanisms such as the link between the glycomodification of immunoglobulins and various autoimmune diseases, notably IgG in rheumatoid arthritis (RA), and has exciting implications for the development of novel diagnostic and therapeutic interventions.

Serum galactosyltransferase isoform changes in rheumatoid arthritis.

OBJECTIVE: To investigate glycosylation changes associated with rheumatoid arthritis (RA) by determining whether there are beta1,4-galactosyltransferase (GTase) isoforms specific to or altered in the serum of patients with RA. Methods. Serum GTase isoform profiles were determined using isoelectric focusing (IEF) in patients with active RA (n = 9), disease controls (DC; n = 9), and healthy individuals (HI; n = 10). RESULTS: There was a highly significant difference (p < 0.0001) between the IEF profiles. The RA IEF profile was significantly (p < 0.0001) different from that of the DC or the HI group. There was, however, no significant difference between the DC and HI profiles. Serum GTase samples from 8/9 RA, 9/9 DC, and 9/10 HI resolved into 2 distinct peaks of activity. The RA isoform profile was associated with an acidic shift. There were no significant differences in the pH value of the first peak; the second peak was found to be significantly more acidic in the RA group (mean pH 5.02) compared to the DC and HI group (mean pH 5.20; p < 0.05). The RA associated isoform constituted a significantly greater proportion of total enzymatic activity in the RA sera (16.1%) compared to DC and HI (13.5%; p < 0.05 and 12.6%; p < 0.01, respectively). RA and HI serum GTase desialylation resulted in an alkaline shift of the isoforms into similar pH bands: 5.25-5.50, 5.70-5.85, and 6.20-6.40. GTase was found to be on average 75% more active in its desialylated form than in its sialylated state. CONCLUSION: RA is associated with a differential expression of GTase isoforms. This may be due to increased hypersialylation, which has the potential to adversely affect the catalytic activity of the enzyme, thus providing a possible mechanism for posttranslational regulation of GTase activity in RA.