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Determination of insulin autoantibodies using surface plasmon resonance: A screening study of newly diagnosed type 1 diabetes patients
Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
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2008 (English)Manuscript (preprint) (Other academic)
Abstract [en]

We have investigated the screening potential of a surface plasmon resonance (SPR)-based indirectcompetitive immunoassay for quantification of insulin autoantibodies (IAA) in sera from childrennewly diagnosed with type 1 diabetes (T1D), using a radioimmunoassay (RIA) as reference technique.The two methods agreed well with respect to sample classification of 54 sera from newly diagnosedT1D children and 32 reference sera from non-diabetic children. Interestingly, five samples from newlydiagnosed T1D patients classified as IAA-negative according to RIA were IAA-positive with the SPRbasedassay, suggesting that the SPR-based assay might provide a higher sensitivity than the referenceRIA. However, 14 percent of the analyzed samples (five samples from non-diabetics and seven fromnewly diagnosed T1D patients) gave rise to anomalously high and easily distinguishable responses withthe SPR-based method, precluding IAA-quantification. A considerable part of the paper is devoted to adiscussion of possible causes of these anomalous responses. They were not due to temporary changesin the status of the patients, such as infections at the time of sampling, and also not related tocomplement activation. It is speculated whether a plausible explanation should instead be sought in theexistence of anti-idiotypic antibodies to IAA.

Place, publisher, year, edition, pages
2008.
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:liu:diva-12470OAI: oai:DiVA.org:liu-12470DiVA: diva2:182
Available from: 2008-09-06 Created: 2008-09-06 Last updated: 2015-10-05Bibliographically approved
In thesis
1. Interaction Studies in Complex Fluids with Optical Biosensors
Open this publication in new window or tab >>Interaction Studies in Complex Fluids with Optical Biosensors
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis interactions in complex fluids, such as serum and meat juice, were analysed with optical biosensor techniques.

Panels of lectins immobilised on gold surfaces were used for investigation of differences in protein glycosylation pattern in sera and meat juices between various species. The present panel was also used for investigation of global glycosylation changes of serum proteins in type 1 diabetes patients. Biorecognition was evaluated with null ellipsometry and scanning ellipsometry combined with multivariate data analysis techniques (MVDA). Principal component analysis (PCA) showed that the lectin panel enabled discrimination between sera from the different species as well as for the different meat juices. The results also indicate that there is a measurable global alteration in glycosylation pattern of serum proteins in type 1 diabetic patients compared to healthy subjects. Using an artificial neuronal net (ANN), it was also possible to correctly categorise unknown serum samples into their respective class or group. The analytical potential of combining information from lectin panels with multivariate data analysis was thereby demonstrated.

Also, a sensitive and specific method based on surface plasmon resonance (SPR) for detection of insulin autoantibodies (IAA) in serum samples from individuals at high risk of developing type 1 diabetes (T1D) has been developed. When measuring trace molecules, such as autoantibodies, in undiluted sera with label-free techniques like SPR, non-specific adsorption of matrix proteins to the sensor surface is often a problem, since it causes a signal that masks the analyte response. The developed method is an indirect competitive immunoassay designed to overcome these problems. Today, IAA is mainly measured in radio immunoassays (RIAs), which are time consuming and require radioactively labelled antigen. With our SPR-based immunoassay the overall assay time is reduced by a factor of >100 (from 4 days to 50 min), while sensitivity is maintained at a level comparable to that offered by RIA. Finally, the assay was used in a screening study of newly diagnosed type 1 diabetes patients and non-diabetic subjects.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. 70 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1195
Keyword
Type 1 diabetes, Insulin, Lectin panel, Ellipsometry, Meat juice, Serum proteins
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-14694 (URN)978-91-7394-852-5 (ISBN)
Public defence
2008-09-19, Planck, Fysikhuset, Campus Norrköping, Linköpings universitet, Linköping, 10:15 (English)
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Supervisors
Available from: 2008-09-26 Created: 2008-09-19 Last updated: 2009-04-24Bibliographically approved

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Carlsson, JennyGullstrand, CamillaWestermark, GunillaLudvigsson, JohnnyEnander, KarinLiedberg, Bo

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Carlsson, JennyGullstrand, CamillaWestermark, GunillaLudvigsson, JohnnyEnander, KarinLiedberg, Bo
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Applied PhysicsThe Institute of TechnologyPediatricsFaculty of Health SciencesCell BiologyDepartment of Paediatrics in LinköpingSensor Science and Molecular Physics
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