scholarly journals Searching for a placental derived ES-62-like molecule to explain rheumatoid arthritis amelioration in pregnancy

2014 ◽  
Vol 6 (1) ◽  
Author(s):  
Craig D. Scoville ◽  
Devon Rasmussen

The majority of women with rheumatoid arthritis (RA) experience disease amelioration during pregnancy for unclear reasons. One possible explanation pursued and described here is whether the placenta produces a protein similar to the immunomodulating protein, ES-62, excreted by filarial nematodes. This protein has also been shown to reduce disease activity in animal models of RA. Eleven human placentas were prepared and a polyclonal anti-ES-62 antiserum was used to identify if any ES-62-like molecule exists from human placental tissues. Any bands identified were then excised from the gel and sent for mass spectrometry and protein identification. The anti-serum showed consistent cross reactivity with the heavy chain from immunoglobulin G (IgG) from the eleven human placentas by mass spectrometry. No primary sequence homology between the heavy chain of IgG and ES-62 was identified. The placenta does not produce an ES-62-like molecule. However the binding of the antiserum to the Fc region of IgG suggests that this may be a possible mechanism for rheumatoid factor production in some patients with chronic filarial infections.

Author(s):  
Ivana Stojanovic ◽  
Mirjana Dimitrijevic ◽  
Marta Vives-Pi ◽  
Maria Jose Mansilla ◽  
Irma Pujol-Autonell ◽  
...  

Author(s):  
Rocco J. Rotello ◽  
Timothy D. Veenstra

: In the current omics-age of research, major developments have been made in technologies that attempt to survey the entire repertoire of genes, transcripts, proteins, and metabolites present within a cell. While genomics has led to a dramatic increase in our understanding of such things as disease morphology and how organisms respond to medications, it is critical to obtain information at the proteome level since proteins carry out most of the functions within the cell. The primary tool for obtaining proteome-wide information on proteins within the cell is mass spectrometry (MS). While it has historically been associated with the protein identification, developments over the past couple of decades have made MS a robust technology for protein quantitation as well. Identifying quantitative changes in proteomes is complicated by its dynamic nature and the inability of any technique to guarantee complete coverage of every protein within a proteome sample. Fortunately, the combined development of sample preparation and MS methods have made it capable to quantitatively compare many thousands of proteins obtained from cells and organisms.


2020 ◽  
Vol 58 (6) ◽  
pp. 1002-1009 ◽  
Author(s):  
Caroline Le Goff ◽  
Jordi Farre-Segura ◽  
Violeta Stojkovic ◽  
Patrice Dufour ◽  
Stéphanie Peeters ◽  
...  

AbstractHistorically, the determination of low concentration analytes was initially made possible by the development of rapid and easy-to-perform immunoassays (IAs). Unfortunately, typical problems inherent to IA technologies rapidly appeared (e.g. elevated cost, cross-reactivity, lot-to-lot variability, etc.). In turn, liquid chromatography tandem mass spectrometry (LC-MS/MS) methods are sensitive and specific enough for such analyses. Therefore, they would seem to be the most promising candidates to replace IAs. There are two main choices when implementing a new LC-MS/MS method in a clinical laboratory: (1) Developing an in-house method or (2) purchasing ready-to-use kits. In this paper, we discuss some of the respective advantages, disadvantages and mandatory requirements of each choice. Additionally, we also share our experiences when developing an in-house method for cortisol determination and the implementation of an “ready-to-use” (RTU) kit for steroids analysis.


Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 160
Author(s):  
Evelyn Rampler ◽  
Gerrit Hermann ◽  
Gerlinde Grabmann ◽  
Yasin El Abiead ◽  
Harald Schoeny ◽  
...  

Non-targeted analysis by high-resolution mass spectrometry (HRMS) is an essential discovery tool in metabolomics. To date, standardization and validation remain a challenge. Community-wide accepted cost-effective benchmark materials are lacking. In this work, we propose yeast (Pichia pastoris) extracts derived from fully controlled fermentations for this purpose. We established an open-source metabolite library of >200 identified metabolites based on compound identification by accurate mass, matching retention times, and MS/MS, as well as a comprehensive literature search. The library includes metabolites from the classes of (1) organic acids and derivatives (2) nucleosides, nucleotides, and analogs, (3) lipids and lipid-like molecules, (4) organic oxygen compounds, (5) organoheterocyclic compounds, (6) organic nitrogen compounds, and (7) benzoids at expected concentrations ranges of sub-nM to µM. As yeast is a eukaryotic organism, key regulatory elements are highly conserved between yeast and all annotated metabolites were also reported in the human metabolome database (HMDB). Orthogonal state-of-the-art reversed-phase (RP-) and hydrophilic interaction chromatography mass spectrometry (HILIC-MS) non-targeted analysis and authentic standards revealed that 104 out of the 206 confirmed metabolites were reproducibly recovered and stable over the course of three years when stored at −80 °C. Overall, 67 out of these 104 metabolites were identified with comparably stable areas over all three yeast fermentation and are the ideal starting point for benchmarking experiments. The provided yeast benchmark material enabled not only to test for the chemical space and coverage upon method implementation and developments but also allowed in-house routines for instrumental performance tests. Transferring the quality control strategy of proteomics workflows based on the number of protein identification in HeLa extracts, metabolite IDs in the yeast benchmarking material can be used as metabolomics quality control. Finally, the benchmark material opens new avenues for batch-to-batch corrections in large-scale non-targeted metabolomics studies.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1450.2-1450
Author(s):  
H. Bjørngaard ◽  
H. Koksvik ◽  
B. Jakobsen ◽  
M. Wallenius

Background:Treat to target is a goal, also in pregnant women with Rheumatoid arthritis (1). There is increasing evidence on safe use with TNF inhibitors during pregnancy. Adjusted use of TNF inhibitors preconception and throughout pregnancy may stabilize disease activity and prevent flares (2). Low disease activity is also beneficial for the fetus.Objectives:To study the use of TNF-inhibitors among women with Rheumatic arthritis during and after pregnancy.Methods:RevNatus is a Norwegian, nationwide quality register that monitors treatment of inflammatory rheumatic diseases before, during and after pregnancy. Data from RevNatus in the period October 2017 to October 2019 was used to map the use of all types of TNF inhibitors among 208 women with rheumatoid arthritis, diagnosed by the ACR/EULAR criteria. The use of medication was reported at the time of visit in outpatient clinic. The frequency of use of TNF inhibitors registered at seven timepoints from pre-pregnancy to twelve months after delivery.Results:The use of medication was reported at each visit for all the women with rheumatoid arthritis. Most of the women were not using TNF inhibitors before and beyond conception. Most of the women continuing TNF inhibitors beyond conception used certolizumab or etanercept. Adalimumab and infliximab were used in pregnancy (tabell 1).Tabell 1.certoliz-umabetane-rceptadalim-umabgolim-umabinflixi-mabNo TNF-inhibitorBefore pregnancyn=10521% (22)9% (10)3% (3)1% (1)66% (69)1.trimestern=8119% (15)10% (8)71% (58)2.trimestern=8810% (9)10% (9)80% (70)3.trimestern=9111% (10)5% (5)83% (76)6 weeks post partum n=9622% (21)13% (13)1% (1)1% (1)63% (60)6 months post partum n=8824% (21)18% (16)4% (4)1% (1)53% (46)12 months post partum n=8421% (18)17% (15)7% (6)2% (2)53% (43)Conclusion:Most of the women with rheumatic arthritis were not treated with TNF inhibitors before or in pregnancy. Women with rheumatic arthritis that continuing treatment with TNF inhibitors through pregnancy were using certilozumab and etanercept.References:[1]Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. 2016;75(5):795-810.[2]van den Brandt S, Zbinden A, Baeten D, Villiger PM, Ostensen M, Forger F. Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients. Arthritis Res Ther. 2017;19(1):64.Disclosure of Interests:None declared


2017 ◽  
Vol 73 (11) ◽  
pp. 910-920 ◽  
Author(s):  
David Brent Langley ◽  
Ben Crossett ◽  
Peter Schofield ◽  
Jenny Jackson ◽  
Mahdi Zeraati ◽  
...  

Duck egg lysozyme (DEL) is a widely used model antigen owing to its capacity to bind with differential affinity to anti-chicken egg lysozyme antibodies. However, no structures of DEL have so far been reported, and the situation had been complicated by the presence of multiple isoforms and conflicting reports of primary sequence. Here, the structures of two DEL isoforms from the eggs of the commonly used Pekin duck (Anas platyrhynchos) are reported. Using structural analyses in combination with mass spectrometry, non-ambiguous DEL primary sequences are reported. Furthermore, the structures and sequences determined here enable rationalization of the binding affinity of DEL for well documented landmark anti-lysozyme antibodies.


1998 ◽  
Vol 19 (6) ◽  
pp. 1006-1014 ◽  
Author(s):  
Thierry Rabilloud ◽  
Sylvie Kieffer ◽  
Vincent Procaccio ◽  
Mathilde Louwagie ◽  
Paul L. Courchesne ◽  
...  

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