ECTRIMS eLearning

Affinity proteomics for array based profiling of autoantibody repertoires
ECTRIMS Learn. Nilsson P. 10/11/18; 231932; 183
Peter Nilsson
Peter Nilsson
Contributions
Abstract

Abstract: 183

Type: Hot Topic

Abstract Category: N/A

Introduction: The general understanding of the global reactivity patterns in the human autoantibody repertoires is still at an early phase. More and more diseases and conditions are speculated to have autoimmune components but very few novel targets are clearly associated to disease conditions.
Objectives: In order to explore autoantibody reactivities and to screen for novel autoantigens within multiple sclerosis and other neurodegenerative disorders, we have for several years developed and utilized various formats of protein microarrays.
Methods: Through a combination of various planar and bead-based array formats, including an array with 42.000 protein fragments representing 19.000 unique proteins, assays are set up for broad screening studies as well as targeted analysis for verification and validation of initial findings. The latter format utilize a bead based format where 384 samples can be analyzed in parallel on 384 antigens. The antigens have a median length of approximately 80 amino acids and are produced in E. coli within the Human Protein Atlas (www.proteinatlas.org).
Results: We have previously, in collaboration with Tomas Olsson and Ingrid Kockum et al at Karolinska Institutet, through array-based profiling of autoantibodies identified the calcium activated chloride-channel protein Anoctamin 2 (ANO2) as an autoantigen associated to a subgroup of multiple sclerosis patients (Ayoglu 2013, 2016). Within a follow up effort of autoantibody profiling in large number of CSF and plasma samples in a broad neurodegenerative context as well as within healthy individuals, are we now comparing and exploring the global autoantibody repertoires of brain associated proteins in multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia as well as in psychiatric disorders.
Conclusions: We see in general a large degree of heterogeneity between individuals and within diseases and also often relatively high numbers of antigens targeted by each individuals repertoires of IgGs, which is also the case for healthy individuals. There is certainly a need for careful and extensive characterization of identified autoantigens in order to understand the disease associated mechanisms.
Ayoglu et al 2013. Autoantibody profiling in multiple sclerosis using arrays of human protein fragments. Mol Cell Proteomics.
Ayoglu et al 2016. Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proc Natl Acad Sci USA.
Disclosure: Peter Nilsson: Nothing do disclose

Abstract: 183

Type: Hot Topic

Abstract Category: N/A

Introduction: The general understanding of the global reactivity patterns in the human autoantibody repertoires is still at an early phase. More and more diseases and conditions are speculated to have autoimmune components but very few novel targets are clearly associated to disease conditions.
Objectives: In order to explore autoantibody reactivities and to screen for novel autoantigens within multiple sclerosis and other neurodegenerative disorders, we have for several years developed and utilized various formats of protein microarrays.
Methods: Through a combination of various planar and bead-based array formats, including an array with 42.000 protein fragments representing 19.000 unique proteins, assays are set up for broad screening studies as well as targeted analysis for verification and validation of initial findings. The latter format utilize a bead based format where 384 samples can be analyzed in parallel on 384 antigens. The antigens have a median length of approximately 80 amino acids and are produced in E. coli within the Human Protein Atlas (www.proteinatlas.org).
Results: We have previously, in collaboration with Tomas Olsson and Ingrid Kockum et al at Karolinska Institutet, through array-based profiling of autoantibodies identified the calcium activated chloride-channel protein Anoctamin 2 (ANO2) as an autoantigen associated to a subgroup of multiple sclerosis patients (Ayoglu 2013, 2016). Within a follow up effort of autoantibody profiling in large number of CSF and plasma samples in a broad neurodegenerative context as well as within healthy individuals, are we now comparing and exploring the global autoantibody repertoires of brain associated proteins in multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia as well as in psychiatric disorders.
Conclusions: We see in general a large degree of heterogeneity between individuals and within diseases and also often relatively high numbers of antigens targeted by each individuals repertoires of IgGs, which is also the case for healthy individuals. There is certainly a need for careful and extensive characterization of identified autoantigens in order to understand the disease associated mechanisms.
Ayoglu et al 2013. Autoantibody profiling in multiple sclerosis using arrays of human protein fragments. Mol Cell Proteomics.
Ayoglu et al 2016. Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proc Natl Acad Sci USA.
Disclosure: Peter Nilsson: Nothing do disclose

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