Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

Abstract Background Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls. Methods In order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC–MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90). Results We observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters. Conclusions This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.

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Proteomics analysis reveals differential pattern of widespread protein expression and novel role of histidine-rich glycoprotein and lipopolysaccharide-binding protein in rheumatoid arthritis

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2017.12.075 ◽

2018 ◽

Vol 109 ◽

pp. 704-710 ◽

Cited By ~ 10

Author(s):

Doojin Kim ◽

Sora Mun ◽

Jiyeong Lee ◽

Arum Park ◽

AeEun Seok ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Protein Expression ◽

Binding Protein ◽

Lipopolysaccharide Binding Protein ◽

Proteomics Analysis ◽

Differential Pattern ◽

Lipopolysaccharide Binding

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Plasma lipopolysaccharide binding protein and bactericidal/permeability increasing factor in CRF and HD patients.

Journal of the American Society of Nephrology ◽

10.1681/asn.v73479 ◽

1996 ◽

Vol 7 (3) ◽

pp. 479-487

Author(s):

B J Pereira ◽

S Sundaram ◽

B Snodgrass ◽

P Hogan ◽

A J King

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Plasma Levels ◽

Cytokine Production ◽

Binding Protein ◽

Interleukin 1 ◽

Healthy Controls ◽

Lipopolysaccharide Binding Protein ◽

Alpha Production ◽

Lipopolysaccharide Binding

The recent characterization of lipopolysaccharide binding protein (LBP) and bactericidal/permeability increasing factor (BPI) have provided the opportunity to examine the natural factors that regulate cytokine production in response to endotoxin in patients on hemodialysis (HD). Whole blood was collected in EDTA from 28 undialyzed patients with chronic renal failure (undialyzed CRF), 36 patients on chronic HD (HD) and 15 healthy controls, and plasma levels of LBP and BPI were measured by a sandwich ELISA. Plasma LBP levels in undialyzed patients with CRF (P = 0.04) and patients on HD (P = 0.01) were significantly higher than those in healthy controls, but not significantly different from each other. Plasma BPI levels in undialyzed patients with CRF and patients on HD were not significantly different from those in healthy controls. There was no correlation between serum creatinine and plasma levels of either LBP or BPI. Peripheral blood mononuclear cells (PBMC) were harvested from healthy volunteers by FLcoll-Hypaque separation, and 0.125 mL of 10 x 10(6)/mL suspensions were incubated with 0.125 mL of test plasma (containing different LBP/BPI ratios) and 0.25 mL of RPMI, containing 1 ng/mL of endotoxin, for 24 h at 37 degrees C. Samples were subjected to three freeze-thaw cycles, and total interleukin-1 receptor antagonist (IL-1Ra) or interleukin-1 alpha (IL-1 alpha) production was measured by a specific non-crossreactive RIA. The results of this study showed: (1) IL-1Ra production by endotoxin-stimulated PBMC incubated with pooled plasma from HD patients with LBP/BPI ratios of 11 x 10(2), 167 x 10(2), 379 x 10(2), and 778 x 10(2), respectively was 1466 +/- 195 pg, 3105 +/- 462 pg, 8179 +/- 1020 pg, and 4770 +/- 1185 pg (P < 0.001); (2) Paired plasma collected before dialysis (predialysis) and at 15 min after the start of dialysis (15 minute) with cellulose membranes showed a negligible change in plasma LBP levels (-3 +/- 5%), but a 6681 +/- 1788% increase in plasma BPI levels. Consequently, compared with predialysis plasma, there was a 35 +/- 6% decrease in endotoxin-stimulated IL-1 alpha production by PBMC incubated with plasma drawn at 15 min (P = 0.001); (3) Compared with the PBMC incubated with predialysis plasma from HD patients, there was a 39 +/- 5%, 53 +/- 5%, and 60 +/- 5% decrease in endotoxin-stimulated IL-1 alpha production in the presence of 1 ng/ mL, 10 ng/mL, or 1 microgram/mL of recombinant BPI, respectively (P < 0.003). These results suggest that the plasma LBP:BPI ratio could influence cytokine production in response to bacterial endotoxin; the high LBP:BPI ratios observed in patients with chronic renal failure probably imparts an increased susceptibility to endotoxin-stimulated cytokine production; and natural or pharmacological increases in plasma BPI levels and the consequent decrease in LBP:BPI ratios could attenuate this susceptibility to endotoxin-stimulated cytokine production.

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Autoantibodies against citrullinated-lipopolysaccharide binding protein as a novel biomarker in seronegative rheumatoid arthritis

10.21203/rs.3.rs-31058/v1 ◽

2020 ◽

Author(s):

Xiaozhen Zhao ◽

Yuling Chen ◽

Yongjing Cheng ◽

Wen Wen ◽

Yuhui Li ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Immune Responses ◽

Binding Protein ◽

Disease Onset ◽

Enzyme Linked Immunosorbent Assay ◽

Lipopolysaccharide Binding Protein ◽

High Incidence ◽

Citrullinated Protein ◽

Citrullinated Antigen ◽

Lipopolysaccharide Binding

Abstract Background A specific feature of rheumatoid arthritis is the presence of citrullinated antigen and production of anti-citrullinated protein autoantibodies (ACPA) which can appear years prior to disease onset to trigger immune responses. In this study, the serum citrulline-containing antigens from RA patients were screened and the significance of the antibodies against citrullinated lipopolysaccharide binding protein (anti-cLBP) was studied. Methods Polypeptides isolated from the serum of patients with RA were identified by the Orbitrap high-precision proteomic technology. And then the citrulline-containing proteins was demonstrated.We synthesized citrullinated LBP peptide based on its richness and possible antigenity. The levels of anti-cLBP were determined in sera of 100 RA, 27 OA, 20 SLE and 50 healthy controls by indirect enzyme-linked immunosorbent assay (ELISA). Result A total of 11 citrulline-containing antigens were identified in proteins from sera of RA patients. By using citrullinated LBP, the antibodies (anti-cLBP) was detected in RA patients, healthy and disease controls. We found that the levels of anti-cLBP were significantly increased in RA patients. The sensitivity and specificity of anti-cLBP antibody were 28.00% and 95.92%, respectively. In anti-CCP-negative and RF-negative RA patients, the prevalences of anti-cLBP were 19.05% (4/21) and 20.59% (7/34), respectively. In addition, in RA patients of anti-CCP and RF-double negative, anti-cLBP was also detectable in 16.67% (3/18) of the patients. Further analysis of the clinical relevance, we found that anti-cLBP antibody was associated with disease activities in RA. It was noticed that the level of anti-cLBP was closely related with a high incidence of infection in patients with RA. Conclusion Anti-cLBP autoantibody is a novel biomarker in RA, especially in seronegative RA, and associated with disease severity.

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Molecular cloning of cDNA for lipopolysaccharide-binding protein from the hemolymph of the American cockroach, Periplaneta americana. Similarity of the protein with animal lectins and its acute phase expression

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)98841-1 ◽

1991 ◽

Vol 266 (20) ◽

pp. 13318-13323

Author(s):

T. Jomori ◽

S. Natori

Keyword(s):

Molecular Cloning ◽

Acute Phase ◽

Periplaneta Americana ◽

Binding Protein ◽

American Cockroach ◽

Lipopolysaccharide Binding Protein ◽

Lipopolysaccharide Binding

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Higher Lipopolysaccharide Binding Protein and Chemerin Concentrations Were Associated with Metabolic Syndrome Features in Pediatric Subjects with Abdominal Obesity during a Lifestyle Intervention

Nutrients ◽

10.3390/nu13020289 ◽

2021 ◽

Vol 13 (2) ◽

pp. 289

Author(s):

Amelia Marti ◽

Isabel Martínez ◽

Ana Ojeda-Rodríguez ◽

María Cristina Azcona-Sanjulian

Keyword(s):

Metabolic Syndrome ◽

Children And Adolescents ◽

Lifestyle Intervention ◽

Abdominal Obesity ◽

Plasma Levels ◽

Intervention Program ◽

Binding Protein ◽

Controlled Trial ◽

Lipopolysaccharide Binding Protein ◽

Lipopolysaccharide Binding

Background: Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (−43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.

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Microbiome-Metabolomics Reveals Prebiotic Benefits of Fucoidan Supplementation in Mice

Journal of Marine Science and Engineering ◽

10.3390/jmse9050505 ◽

2021 ◽

Vol 9 (5) ◽

pp. 505

Author(s):

Jingyi Yuan ◽

Song Qin ◽

Wenjun Li ◽

Yubing Zhang ◽

Yuting Wang ◽

...

Keyword(s):

Lipid Metabolism ◽

Triglyceride Level ◽

Lactobacillus Reuteri ◽

Binding Protein ◽

Serum Triglyceride ◽

Serum Triglyceride Level ◽

Lipopolysaccharide Binding Protein ◽

Lactobacillus Gasseri ◽

Lactobacillus Animalis ◽

Lipopolysaccharide Binding

Fucoidan is a kind of polysaccharide with antitumor and antioxidant properties, which is mainly isolated from brown algae. Although there are many reports about the prebiotic effects of polysaccharides on hosts, there are few reports about the effects of fucoidan on blood biochemical indexes, intestinal microbiome, and metabolic function on healthy hosts. We applied 16S rRNA gene amplicon sequencing and LC-MS/MS metabolomics to evaluate the changes in the gut microbiome and metabolite profiles of fucoidan treatment in mice over 10 weeks. Fucoidan treatment modulated lipid metabolism, including significantly decreasing serum triglyceride level in healthy mice. Fucoidan also significantly inhibited serum lipopolysaccharide-binding protein (LBP) concentration, a biomarker of endotoxemia. Correlation analysis further showed that Lactobacillus animalis populations that were enriched by fucoidan demonstrated significantly negative correlations with serum triglyceride level. The abundance of Lactobacillus gasseri and Lactobacillus reuteri, increased by fucoidan supplementation, demonstrated significantly negative correlation with lipopolysaccharide-binding protein levels. Lactobacillus gasseri also demonstrated significantly positive correlations with three tryptophan-related metabolites, including indoleacrylic acid, 3-indoleacrylic acid, and 5-hydroxytryptamine, which were all increased by fucoidan administration. Combined with the previous evidence, the results indicate that fucoidan exerts prebiotic effects, such as lipid metabolism suppression and metabolic endotoxemia suppression, by modulating the abundance of gut microbiota, such as Lactobacillus animalis, Lactobacillus gasseri, and Lactobacillus reuteri, as well as microbiota-dependent metabolites, such as tryptophan-related metabolites.

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