Immunoproteomic Identification of Noncarbohydrate Antigens Eliciting Graft-Specific Adaptive Immune Responses in Patients with Bovine Pericardial Bioprosthetic Heart Valves

Katherine V. Gates, Qi Xing, Leigh Griffiths

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: This case-control retrospective discovery study is to identify antigenic bovine pericardium (BP) proteins that stimulate graft-specific humoral immune response in patients implanted with glutaraldehyde fixed bovine pericardial (GFBP) heart valves. Experimental design: Banked serum is collected from age- and sex-matched patients who received either a GFBP or mechanical heart valve replacement. Serum IgG is isolated and used to generate poly-polyclonal antibody affinity chromatography columns from each patient. Native and deglycosylated BP protein extracts are separately added to individual patient affinity chromatography columns, with unbound proteins washed through the column. Proteins captured in the affinity chromatography columns are submitted for proteomic identification. Differences between GFBP and mechanical heart valve replacement recipients are analyzed with Gaussian linearized modeling. Results: Carbohydrate antigens overwhelm protein capture in the column, requiring BP protein deglycosylation prior to affinity chromatography. Nineteen BP protein antigens, which stimulated graft-specific IgG production, are identified in patients who received GFBP valve replacements. Identified antigens are significantly over-represented for calcium-binding proteins. Conclusions and clinical relevance: Patients implanted with GFBP valves develop a graft-specific humoral immune response toward BP protein antigens, with 19 specific antigens identified in this work. The molecular functions of over-represented antigens, specifically calcium-binding proteins, may aid in understanding the underlying factors that contribute to structural valve deterioration.

Original languageEnglish (US)
Article number1800129
JournalProteomics - Clinical Applications
DOIs
StateAccepted/In press - Jan 1 2018

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Heart Valves
Adaptive Immunity
Grafts
Glutaral
Transplants
Affinity chromatography
Antigens
Pericardium
Proteins
Affinity Chromatography
Calcium-Binding Proteins
Humoral Immunity
Immunoglobulin G
Antibody Affinity
Design of experiments
Deterioration
Serum
Proteomics
Carbohydrates
Research Design

Keywords

  • antigens
  • deglycosylation
  • heart valves
  • immunoproteomics
  • structural valve deterioration

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

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title = "Immunoproteomic Identification of Noncarbohydrate Antigens Eliciting Graft-Specific Adaptive Immune Responses in Patients with Bovine Pericardial Bioprosthetic Heart Valves",
abstract = "Purpose: This case-control retrospective discovery study is to identify antigenic bovine pericardium (BP) proteins that stimulate graft-specific humoral immune response in patients implanted with glutaraldehyde fixed bovine pericardial (GFBP) heart valves. Experimental design: Banked serum is collected from age- and sex-matched patients who received either a GFBP or mechanical heart valve replacement. Serum IgG is isolated and used to generate poly-polyclonal antibody affinity chromatography columns from each patient. Native and deglycosylated BP protein extracts are separately added to individual patient affinity chromatography columns, with unbound proteins washed through the column. Proteins captured in the affinity chromatography columns are submitted for proteomic identification. Differences between GFBP and mechanical heart valve replacement recipients are analyzed with Gaussian linearized modeling. Results: Carbohydrate antigens overwhelm protein capture in the column, requiring BP protein deglycosylation prior to affinity chromatography. Nineteen BP protein antigens, which stimulated graft-specific IgG production, are identified in patients who received GFBP valve replacements. Identified antigens are significantly over-represented for calcium-binding proteins. Conclusions and clinical relevance: Patients implanted with GFBP valves develop a graft-specific humoral immune response toward BP protein antigens, with 19 specific antigens identified in this work. The molecular functions of over-represented antigens, specifically calcium-binding proteins, may aid in understanding the underlying factors that contribute to structural valve deterioration.",
keywords = "antigens, deglycosylation, heart valves, immunoproteomics, structural valve deterioration",
author = "Gates, {Katherine V.} and Qi Xing and Leigh Griffiths",
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T1 - Immunoproteomic Identification of Noncarbohydrate Antigens Eliciting Graft-Specific Adaptive Immune Responses in Patients with Bovine Pericardial Bioprosthetic Heart Valves

AU - Gates, Katherine V.

AU - Xing, Qi

AU - Griffiths, Leigh

PY - 2018/1/1

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N2 - Purpose: This case-control retrospective discovery study is to identify antigenic bovine pericardium (BP) proteins that stimulate graft-specific humoral immune response in patients implanted with glutaraldehyde fixed bovine pericardial (GFBP) heart valves. Experimental design: Banked serum is collected from age- and sex-matched patients who received either a GFBP or mechanical heart valve replacement. Serum IgG is isolated and used to generate poly-polyclonal antibody affinity chromatography columns from each patient. Native and deglycosylated BP protein extracts are separately added to individual patient affinity chromatography columns, with unbound proteins washed through the column. Proteins captured in the affinity chromatography columns are submitted for proteomic identification. Differences between GFBP and mechanical heart valve replacement recipients are analyzed with Gaussian linearized modeling. Results: Carbohydrate antigens overwhelm protein capture in the column, requiring BP protein deglycosylation prior to affinity chromatography. Nineteen BP protein antigens, which stimulated graft-specific IgG production, are identified in patients who received GFBP valve replacements. Identified antigens are significantly over-represented for calcium-binding proteins. Conclusions and clinical relevance: Patients implanted with GFBP valves develop a graft-specific humoral immune response toward BP protein antigens, with 19 specific antigens identified in this work. The molecular functions of over-represented antigens, specifically calcium-binding proteins, may aid in understanding the underlying factors that contribute to structural valve deterioration.

AB - Purpose: This case-control retrospective discovery study is to identify antigenic bovine pericardium (BP) proteins that stimulate graft-specific humoral immune response in patients implanted with glutaraldehyde fixed bovine pericardial (GFBP) heart valves. Experimental design: Banked serum is collected from age- and sex-matched patients who received either a GFBP or mechanical heart valve replacement. Serum IgG is isolated and used to generate poly-polyclonal antibody affinity chromatography columns from each patient. Native and deglycosylated BP protein extracts are separately added to individual patient affinity chromatography columns, with unbound proteins washed through the column. Proteins captured in the affinity chromatography columns are submitted for proteomic identification. Differences between GFBP and mechanical heart valve replacement recipients are analyzed with Gaussian linearized modeling. Results: Carbohydrate antigens overwhelm protein capture in the column, requiring BP protein deglycosylation prior to affinity chromatography. Nineteen BP protein antigens, which stimulated graft-specific IgG production, are identified in patients who received GFBP valve replacements. Identified antigens are significantly over-represented for calcium-binding proteins. Conclusions and clinical relevance: Patients implanted with GFBP valves develop a graft-specific humoral immune response toward BP protein antigens, with 19 specific antigens identified in this work. The molecular functions of over-represented antigens, specifically calcium-binding proteins, may aid in understanding the underlying factors that contribute to structural valve deterioration.

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