Catalytic antibodies to amyloid β peptide in defense against Alzheimer disease

Chemical Immunology Research Center, University of Texas Houston Medical School, Houston, TX 77030, USA.
Autoimmunity Reviews (Impact Factor: 7.93). 06/2008; 7(5):391-7. DOI: 10.1016/j.autrev.2008.03.004
Source: PubMed

ABSTRACT Immunoglobulins (Igs) that bind amyloid beta peptide (Abeta) are under clinical trials for immunotherapy of Alzheimer disease (AD). We have identified IgMs and recombinant Ig fragments that hydrolyze Abeta. Hydrolysis of peripheral Abeta by the IgMs may induce increased Abeta release from the brain. The catalytic IgMs are increased in AD patients, presumably reflecting a protective autoimmune response. Reduced Abeta aggregation and neurotoxicity attributable to the catalytic function were evident. These findings provide a foundation for development of catalytic Igs for AD immunotherapy.

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Available from: Robert P Friedland, Sep 25, 2015
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    • "Aβ antibody titers were negatively correlated with cognitive status such that more cognitively impaired individuals tended to exhibit higher anti-Aβ IgG titers [71]. Development of immunotherapeutic reagents for AD is based on the expression of specific proteolytic activity by naturally occurring immunoglobulins [74], and hydrolysis of peripheral Aβ consequent to their capture by IgMs may induce increased Aβ clearance from the brain [75]. "
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    ABSTRACT: With the promise of disease modifying treatments, there is a need for more specific diagnosis and prognosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Plasma biomarkers are likely to be utilised to increase diagnostic accuracy and specificity of AD and cognitive decline. Isobaric tags (iTRAQ) and proteomic methods were used to identify potential plasma biomarkers of MCI and AD. Relative protein expression level changes were quantified in plasma of 411 cognitively normal subjects, 19 AD patients and 261 MCI patients. Plasma was pooled into 4 groups including normal control, AD, amnestic single and multiple domain MCI (aMCI), and nonamnestic single and multiple domain MCI (nMCI). Western-blotting was used to validate iTRAQ data. Integrated function and protein interactions were explored using WEB based bioinformatics tools (DAVID v6.7 and STRING v9.0). In at least two iTRAQ replicate experiments, 30 proteins were significantly dysregulated in MCI and AD plasma, relative to controls. These proteins included ApoA1, ApoB100, complement C3, C4b-binding protein, afamin, vitamin D-binding protein precursor, isoform 1 of Gelsolin actin regulator, Ig mmu chain C region (IGHM), histidine-rich glycoprotein and fibrinogen beta and gamma chains. Western-blotting confirmed that afamin was decreased and IGHM was increased in MCI and AD groups. Bioinformatics results indicated that these dysregulated proteins represented a diversity of biological processes, including acute inflammatory response, cholesterol transport and blood coagulation. These findings demonstrate that expression level changes in multiple proteins are observed in MCI and AD plasma. Some of these, such as afamin and IGHM, may be candidate biomarkers for AD and the predementia condition of MCI.
    Proteome Science 01/2014; 12(1):5. DOI:10.1186/1477-5956-12-5 · 1.73 Impact Factor
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    • "Further, anti-DNA antibodies could act principally in RVDs of certain autoimmune diseases. In conclusion, computationally-decided RVD might be useful in optimised, crucial or adjuvant problem-solving and time-saving approach for efficient DNA vaccination (in cases where protein-based microbial vaccines have failed as in HIV and human Parvovirus B19-induced diseases) (Taguchi et al., 2008; Pavlovic et al., 2010). "
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    ABSTRACT: Abstract: Specific entities of naturally-occurring DNA hydrolytic/cytotoxic antibodies (abzymes) are linked to autoimmune and lymphoproliferative disorders. Suggested sequence of underlying activities conform to such entities penetrating the living cells, trans-locating to nucleus and recognising specific binding sites within single- or double-stranded DNA. Their origin is unknown since corresponding immunogens are unidentified. These anti-DNA antibodies could be the organism’s immune response to microbial attack. Their structure, function and pathogenicity were investigated in wet-lab and via bioinformatics in context of Rational Vaccine Designs. This paper offers a comprehensive critical review on the subject in the light of known and newly proposed concepts. Keywords: autoimmune diseases; human immunodeficiency virus; anti-DNA antibodies; DNA vaccine; RVD; rational vaccine design.
    Edited by Neelakanta P, Pavlovic M, Zhuang H, 02/2013: chapter From Pauling’s Abzyme Concept to the New era of Hydrolytic Anti-DNA autoatnibodies: A link to the rational vaccine design?: pages 220-238(18); , ISBN: Special Issue of IJBRA
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    • "These antibodies, now named as "abzymes", were first obtained in 1986 (Pollack, Jacobs, & Schultz, 1986; Tramontano, Janda, & Lerner, 1986), the first example of natural abzymes was IgG found in bronchial asthma patients, cleaving intestinal vasoactive peptide (Paul et al., 1989). Abzyme's properties were discussed in more detail in recent reviews (Belogurov, Kozyr, Ponomarenko, & Gabibov, 2009; Georgy A. Nevinsky & Buneva, 2005; Planque et al., 2008; Taguchi et al., 2008). Abzymes were detected in human organism at a variety of autoimmune and nonautoimmune pathologies (Gabibov, Ponomarenko, Tretyak, Paltsev, & Suchkov, 2006; G. A. Nevinsky & Buneva, 2003), and various peptides, proteins, nucleic acids and oligosaccharides can serve as substrates for the catalytically active antibodies in human and other mammalians (Hanson, Nishiyama, & Paul, 2005; Lacroix-Desmazes et al., 2006). "
    Autoimmune Disorders - Pathogenetic Aspects, 10/2011; , ISBN: 978-953-307-643-0
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