206 research outputs found
Baseline IgG-Fc N-glycosylation profile is associated with long-term outcome in a cohort of early inflammatory arthritis patients
ackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease for which prediction of long-term prognosis from diseaseâs outset is not clinically feasible. The importance of immunoglobulin G (IgG) and its Fc N-glycosylation in inflammation is well-known and studies described its relevance for several autoimmune diseases, including RA. Herein we assessed the association between IgG N-glycoforms and disease prognosis at 2 years in an early inflammatory arthritis cohort.MethodsSera from 118 patients with early inflammatory arthritis naĂŻve to treatment sampled at baseline were used to obtain IgG Fc glycopeptides, which were then analyzed in a subclass-specific manner by liquid chromatography coupled to mass spectrometry (LC-MS). Patients were prospectively followed and a favorable prognosis at 2 years was assessed by a combined index as remission or low disease activity (DAS28 ResultsWe observed a significant association between high levels of IgG2/3 Fc galactosylation (effect 0.627 and adjusted p value 0.036 for the fully galactosylated glycoform H5N4F1; effect â0.551 and adjusted p value 0.04963 for the agalactosylated H3N4F1) and favorable outcome after 2 years of treatment. The inclusion of IgG glycoprofiling in a multivariate analysis to predict the outcome (with HAQ, DAS28, RF, and ACPA included in the model) did not improve the prognostic performance of the model.ConclusionPending confirmation of these findings in larger cohorts, IgG glycosylation levels could be used as a prognostic marker in early arthritis, to overcome the limitations of the current prognostic tools.Proteomic
Imaging Mass Spectrometry Detection of Gangliosides Species in the Mouse Brain following Transient Focal Cerebral Ischemia and Long-Term Recovery
Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18â¶1, d20â¶1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury
Multivariate discovery and replication of five novel loci associated with Immunoglobulin G <i>N</i>-glycosylation
Multivariate analysis methods can uncover the relationship between phenotypic measures characterised by modern omic techniques. Here the authors conduct a multivariate GWAS on IgG N-glycosylation phenotypes and identify 5 novel loci enriched in immune system genes
Association of the IgG N-glycome with the course of kidney function in type 2 diabetes
Introduction Inflammatory processes are thought to
be involved in kidney function decline in individuals
with type 2 diabetes. Glycosylation of immunoglobulin G
(IgG) is an important post-translation process affecting
the inflammatory potential of IgG. We investigated the
prospective relationship between IgG N-glycosylation
patterns and kidney function in type 2 diabetes.
Research design and methods In the DiaGene study,
an all-lines-of-care caseâcontrol study (n=1886) with
mean prospective follow-up of 7.0 years, the association
between 58 IgG N-glycan profiles and estimated
glomerular filtration rate (eGFR) and albumin-to-creatinine
ratio (ACR) per year and during total follow-up was
analyzed. Models were adjusted for clinical variables and
multiple comparisons.
Results Eleven traits were significantly associated with
eGFR change per year. Bisecting GlcNAc in fucosylated and
fucosylated disialylated structures and monosialylation of
fucosylated digalactosylated structures were associated
with a faster decrease of eGFR. Fucosylation of neutral and
monogalactosylated structures was associated with less
eGFR decline per year. No significant associations between
IgG glycans and ACR were found.
Conclusions In type 2 diabetes, we found IgG Nglycosylation patterns associated with a faster decline
of kidney function, reflecting a pro-inflammatory state of
IgG. eGFR, but not ACR, was associated with IgG glycans,
which suggests these associations may represent renal
macroangiopathy rather than microvascular disease
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