Profiling the autoantibody repertoire by serological antigen selection

Govarts

The Journal of Immunology

et al. 2008

An important contribution of B cells and autoantibodies has been demonstrated in the pathogenesis of multiple sclerosis (MS), leading to interest in the use of such autoantibodies as diagnostic or prognostic biomarkers. The objective of this study was to identify novel Ab biomarkers for MS using “serological Ag selection”. Using a phage display library derived from MS brain plaques, we applied serological Ag selection to identify antigenic targets specifically interacting with Abs present in the cerebrospinal fluid (CSF) of 10 relapsing-remitting MS patients. These antigenic targets were further evaluated on a large panel of CSF from 63 other MS patients, 30 patients with other inflammatory disorders, and 64 patients with noninflammatory neurological disorders. A panel of eight antigenic targets was identified that showed a 86% specificity and 45% sensitivity in discriminating MS patients and controls. Four of the antigenic targets showed exclusive reactivity (100% specificity; 23% sensitivity) in the MS group as compared with the control group. Detailed bio-informatic analyses revealed a novel Ag, SPAG16. Among the novel phage peptides identified, novel epitopes were generated from untranslated sequences and out-of-frame sequences. Of 10 relapsing-remitting patients used for serological Ag selection, Ab reactivity toward one of the eight antigenic targets was also demonstrated in serum of 38% CSF-positive patients. Autoantibody profiles against epitopes derived from MS brain tissue could serve as diagnostic markers or form the basis for the identification of a subgroup of MS patients.

Section: Cloning Of a Ms Cdna Library For Pvi Display And Sas Of Phagmentioning

confidence: 99%

Section: Cloning Of a Ms Cdna Library For Pvi Display And Sas Of Phagmentioning

confidence: 99%

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Autoantibody Profiling in Multiple Sclerosis Reveals Novel Antigenic Candidates

Govarts

The Journal of Immunology

et al. 2008

Proteomics Clinical Apps

“…In a recent study, Somers et al [97] validated the use of a powerful molecular approach, serological antigen selection [98], for the study of autoantibodies in the CSF or serum of multiple sclerosis patients. The authors used a normalized cDNA library derived from active chronic multiple sclerosis plaques and directionally cloned and displayed the cDNA repertoires on filamentous phage.…”

Section: Profiling Of the Autoantibody Response In Multiple Sclerosismentioning

confidence: 99%

“…However, these investigations employed random peptide libraries to bind IgGs. One limitation of this technique as compared to the newer approach used by Somers et al [97] is that only antigen mimotopes are picked up and further investigations are necessary to identify the actual antigen. Subsequent studies by the same investigators [101,102] indicated that identical antibodies are present both in the serum and CSF albeit a number of them are particularly enriched in the CSF.…”

Section: Profiling Of the Autoantibody Response In Multiple Sclerosismentioning

confidence: 99%

Proteomic strategies in multiple sclerosis and its animal models

Elkabes

2007

The early and precise diagnosis, the prognosis, and the clinical management of multiple sclerosis, remain a considerable challenge. In recent years, the development of novel and powerful proteomic techniques prompted the use of these approaches for the search of unique biomarkers in the cerebrospinal fluid of multiple sclerosis patients. A few studies have also utilized proteomics to delineate the profile of differentially expressed proteins in animal models of the human disease in order to gain global insights into affected pathways. The identification of differentially expressed proteins may be an initial step in the discovery of novel targets and mechanisms that play critical roles in the pathology of multiple sclerosis. Based on these findings, future investigations may elucidate the events leading to demyelination, axonal damage, and neurodegeneration, providing better insights into mechanisms governing the onset and progression of the disease. Although these proteomic studies provide valuable information, they are also faced with a number of challenges. The present review discusses some of the strengths and limitations of proteomic investigations as applied to multiple sclerosis.

The Use of Phage Display in Neurobiology

Bradbury

2010

CP Neuroscience

Phage display has been extensively used to study protein-protein interactions, receptor- and antibody-binding sites, and immune responses, to modify protein properties, and to select antibodies against a wide range of different antigens. In the format most often used, a polypeptide is displayed on the surface of a filamentous phage by genetic fusion to one of the coat proteins, creating a chimeric coat protein, and coupling phenotype (the protein) to genotype (the gene within). As the gene encoding the chimeric coat protein is packaged within the phage, selection of the phage on the basis of the binding properties of the polypeptide displayed on the surface simultaneously results in the isolation of the gene encoding the polypeptide. This unit describes the background to the technique, and illustrates how it has been applied to a number of different problems, each of which has its neurobiological counterparts. Although this overview concentrates on the use of filamentous phage, which is the most popular platform, other systems are also described.