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Chapter 114 : Detection of Autoantibodies by Using Immobilized Natural and Recombinant Autoantigens

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Abstract:

This chapter focuses on the methodology in purification of recombinant autoantigens used in the authors' laboratories and recent advances in multiplex immunoassays that are suitable for autoantibody detection. Key aspects related to the production of recombinant autoantigens are discussed briefly in this chapter. The construction of recombinant proteins to be used in the detection of autoantibodies should take into consideration the suitability of the construct design and the ease of purification of resulting proteins. Each assay has limitations in terms of determining the sensitivity, specificity, and positive predictive value for the detection of autoantibodies. The chapter focuses on addressable laser bead technology and recent experience with it in a clinical laboratory setting with addressable laser bead immunoassays (ALBIA). In a clinical service laboratory setting an autoantigen panel based on ALBIA was evaluated and compared to the routine diagnostic protocol, which analyzed 870 sequential unselected sera received over a 6-month period. In this study, the sera were submitted primarily by clinicians who were considering a diagnosis of systemic rheumatic disease. Unselected sera from various disease cohorts were also studied to determine if the frequency of autoantibodies as detected by the ALBIA was consistent with the published frequency of autoantibodies. Taken together, there are advantages and challenges that come with the adoption of the ALBA platform to detect autoantibodies. There are now several ALBIA kits on the market that detect eight or more autoantibodies relevant to systemic rheumatic diseases.

Citation: Chan E, Burlingame R, Fritzler M. 2006. Detection of Autoantibodies by Using Immobilized Natural and Recombinant Autoantigens, p 1019-1026. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch114

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FIGURE 1

Enhanced expression of recombinant proteins is illustrated by the effect on the bacterial host. A construct, pET-p115, was transformed into either bacterial strain JM109(DE3) or Rosetta(DE3), and recombinant proteins were produced with the transformed bacteria using the same culture medium (2YT) and conditions. To cultured bacteria was added 1 mM isopropyl-β-D-thiogalactopyranoside (IPTG) at time zero, and cells were harvested as pellets after 1 or 2 h, solubilized in gel sample buffer, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis using a 5% acrylamide gel. Proteins were detected by Coomassie brilliant blue G-250 stain. Note that the recombinant JM109(DE3) culture generated major products of ˜60 kDa (arrowhead) plus other lower-molecular-mass products, whereas the Rosetta culture yielded major products (arrow) corresponding to the native protein.

Citation: Chan E, Burlingame R, Fritzler M. 2006. Detection of Autoantibodies by Using Immobilized Natural and Recombinant Autoantigens, p 1019-1026. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch114
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Tables

Generic image for table
TABLE 1

Reactivity of sera from 100 PBC patients in ALBIA

Citation: Chan E, Burlingame R, Fritzler M. 2006. Detection of Autoantibodies by Using Immobilized Natural and Recombinant Autoantigens, p 1019-1026. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch114
Generic image for table
TABLE 2

Comparison of ELISA and ALBIA detection of anti-ribosomal P autoantibodies in 30 sera

Citation: Chan E, Burlingame R, Fritzler M. 2006. Detection of Autoantibodies by Using Immobilized Natural and Recombinant Autoantigens, p 1019-1026. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch114
Generic image for table
TABLE 3

Frequency of autoantibodies detected by INOVA QUANTA Plex assay in cohorts of patients with systemic rheumatic diseases, those with multiple sclerosis, and controls

Citation: Chan E, Burlingame R, Fritzler M. 2006. Detection of Autoantibodies by Using Immobilized Natural and Recombinant Autoantigens, p 1019-1026. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch114
Generic image for table
TABLE 4

Advantages, challenges, and opportunities relating to new array technologies

Citation: Chan E, Burlingame R, Fritzler M. 2006. Detection of Autoantibodies by Using Immobilized Natural and Recombinant Autoantigens, p 1019-1026. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch114

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