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Published on: November 23, 2013
Redox-reactive autoantibodies in cerebrospinal fluids
John A McIntyre1, Ronald L Hamilton, Steven T DeKosky
1HLA-Vascular Biology Laboratory, St. Francis Hospital & Health Care Centers, 1500 Albany Street, 1109, Beech Grove, IN 46107, USA. john.mcintyre@ssfhs.org
Annals of the New York Academy of Sciences
|September 6, 2007
Summary
Researchers discovered novel redox autoantibodies in cerebrospinal fluid, crucial for immune homeostasis. These antibodies, absent in Alzheimer's disease (AD) patients, suggest a significant immune dysfunction in AD.
Area of Science:
- Neuroimmunology
- Oxidative Stress Biology
Background:
- Neurodegenerative diseases like Alzheimer's are linked to oxidative stress and altered metal concentrations.
- The role of redox-reactive autoantibodies in cerebrospinal fluid (CSF) remains largely unexplored.
Purpose of the Study:
- To investigate the presence and characteristics of redox-reactive autoantibodies in the CSF of Alzheimer's disease (AD) patients.
- To differentiate these novel autoantibodies from previously described natural and hidden autoantibodies.
Main Methods:
- Analysis of cerebrospinal fluid from autopsy-confirmed Alzheimer's disease patients and normal individuals.
- In vitro oxidation-reduction (redox) reactions to assess autoantibody recognition.
- Immunochemical assays to determine autoantibody isotype (IgG, IgM, IgA) and reversibility.
Main Results:
- A novel family of autoantibodies recognizing autoantigens after in vitro redox reactions was identified in normal individuals' blood and CSF.
- These redox autoantibodies are not detected by conventional immunoassays.
- In CSF, redox autoantibodies were exclusively IgG and could be reversible in some patients.
- A proposed mechanism involves redox-driven nitrosylation within the antibody's complementarity-determining regions (CDR).
Conclusions:
- The evolutionary persistence of redox autoantibodies suggests essential physiological roles in immunological homeostasis.
- Their absence or altered presence in Alzheimer's disease indicates a potential immune system dysfunction specific to the disease.
- Redox autoantibodies represent a new class of autoantibodies with potential diagnostic implications for neurodegenerative diseases.
