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Correlation and characterization of ...

Foreman, Angela Lee.

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Correlation and characterization of antibody presence and idiotype variable region in primary biliary cirrhosis.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Correlation and characterization of antibody presence and idiotype variable region in primary biliary cirrhosis./
Author:	Foreman, Angela Lee.
Description:	88 p.
Notes:	Adviser: Judy Van de Water.
Contained By:	Dissertation Abstracts International68-04B.
Subject:	Health Sciences, Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3261153

Correlation and characterization of antibody presence and idiotype variable region in primary biliary cirrhosis.
Foreman, Angela Lee.

Correlation and characterization of antibody presence and idiotype variable region in primary biliary cirrhosis. - 88 p.

Adviser: Judy Van de Water.

Thesis (Ph.D.)--University of California, Davis, 2007.

The enigma of autoimmune disease has baffled researchers for many decades, especially of the presence of auto antigens specific for self antigens. As an autoimmune disease of the liver, primary biliary cirrhosis (PBC), has been unique in that it overlaps two categories of autoimmune diseases encompassing both organ-specific autoimmune disease such as tyroiditis, and systemic autoimmune disease such as systemic lupus erythromatus in which a target organ of destruction is the liver with non-organ specific circulating autoantibodies. In the case of PBC, the systemic presence of circulating anti-mitochondrial antibodies (AMA) are primarily directed against the major auto-antigen, the E2 subunit of pyruvate dehydrogenase complex enzyme (PDC-E2) within the inner mitochondrial membranes, especially in the biliary epithelial cells (BEC) in the liver. We therefore examined the antibody receptors, more specifically IgM as patients with PBC were observed to have high titer IgM, a phenomenon that suggests evidence of B-cell dysregulation. The initial studies examined the autoantibody variable region through the application of the 5' Rapid Amplification of cDNA Ends (5'RACE) in which the IgM from a patient with PBC and a healthy control were amplified. This preliminary study resulted in the demonstration of a 37% difference in the variability of the IgM variable region within the unique gene segments suggesting an oligoclonal pattern for variable gene usage in patients with PBC. To determine total gene usage, we next analyzed the IgM, IgG and IgA bell cell receptor (BCR) repertoire in PBC patients by means of quantitative RT-PCR and CDR3-spectratyping with Immunoscope technology. However, no common expansions within the CDR3 region were found intraindividually between IgG, IgA and IgM, and between patients. In conclusion, Immunoscope technology does provide, for the first time, a sensitive and rapid method for detailed immunoglobulin gene usage analysis in peripheral B cells from PBC patients. This study failed to demonstrate preferential B cell rearrangements in the blood of patients with PBC, but this technology may be more successful if applied to the analysis of compartmental B cells (ie liver infiltrating B cells).Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Correlation and characterization of antibody presence and idiotype variable region in primary biliary cirrhosis.
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100 1 $a Foreman, Angela Lee. $3 1267699
245 1 0 $a Correlation and characterization of antibody presence and idiotype variable region in primary biliary cirrhosis.
300 $a 88 p.
500 $a Adviser: Judy Van de Water.
500 $a Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2234.
502 $a Thesis (Ph.D.)--University of California, Davis, 2007.
520 $a The enigma of autoimmune disease has baffled researchers for many decades, especially of the presence of auto antigens specific for self antigens. As an autoimmune disease of the liver, primary biliary cirrhosis (PBC), has been unique in that it overlaps two categories of autoimmune diseases encompassing both organ-specific autoimmune disease such as tyroiditis, and systemic autoimmune disease such as systemic lupus erythromatus in which a target organ of destruction is the liver with non-organ specific circulating autoantibodies. In the case of PBC, the systemic presence of circulating anti-mitochondrial antibodies (AMA) are primarily directed against the major auto-antigen, the E2 subunit of pyruvate dehydrogenase complex enzyme (PDC-E2) within the inner mitochondrial membranes, especially in the biliary epithelial cells (BEC) in the liver. We therefore examined the antibody receptors, more specifically IgM as patients with PBC were observed to have high titer IgM, a phenomenon that suggests evidence of B-cell dysregulation. The initial studies examined the autoantibody variable region through the application of the 5' Rapid Amplification of cDNA Ends (5'RACE) in which the IgM from a patient with PBC and a healthy control were amplified. This preliminary study resulted in the demonstration of a 37% difference in the variability of the IgM variable region within the unique gene segments suggesting an oligoclonal pattern for variable gene usage in patients with PBC. To determine total gene usage, we next analyzed the IgM, IgG and IgA bell cell receptor (BCR) repertoire in PBC patients by means of quantitative RT-PCR and CDR3-spectratyping with Immunoscope technology. However, no common expansions within the CDR3 region were found intraindividually between IgG, IgA and IgM, and between patients. In conclusion, Immunoscope technology does provide, for the first time, a sensitive and rapid method for detailed immunoglobulin gene usage analysis in peripheral B cells from PBC patients. This study failed to demonstrate preferential B cell rearrangements in the blood of patients with PBC, but this technology may be more successful if applied to the analysis of compartmental B cells (ie liver infiltrating B cells).
590 $a School code: 0029.
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710 2 $a University of California, Davis. $3 1018682
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856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3261153