Antibodies, anti-nucleic acid

DeHoratius RJ, Pillarisetty R, Messner RP, Talal N (1975) Anti-nucleic acid antibodies in systemic lupus erythematosus patients and their families. Incidence and correlation with lymphocytotoxic antibodies. J Clin Invest, 56 1149-1154. 

Steinberg, A. D., Pincus, T., Talal, N. The pathogenesis of autoimmunity in New Zealand mice. III. Factors influencing the formation of anti-nucleic acid antibodies. Immunology 20, 523-531 (1971). 

Some pathogens invade, survive and proliferate within host cells. These include viruses, bacteria and parasites. Viruses are unique since to proliferate they require the nucleic acid and protein synthetic machinery of the infected cells. Hence, once the virus has infected the host cell, the most effective means of killing the virus is to kill the infected cell. Viruses that escape from the dead host cell are neutralised by binding to the antibodies, and the anti-body-virus complex is phagocytosed by macrophages. 

Figure 2.8. Scheme of a chimeric peptide with examples for each of the distinct domains. 0X26, anti-rat transferrin receptor monoclonal antibody (mAh) 84-15, anti-human insulin receptor mAh cHSA, cationized human serum albumin VIP, vasoactive intestinal polypeptide DALDA, dermorphin analogue NGF, nerve growth factor BDNF, brain-derived neurotrophic factor PNA, peptide nucleic acid (3-gal, (3-galactosidase. 

Fig. 30. Detection of mRNA on a membrane or in situ with labeled gene probes. A Detection of mRNA with a fluorescein-labeled single stranded nucleic acid probe, using POD-conjugated anti-fluorescein antibody. B Use of two gene probes labeled with different molecules (fluorescein and digoxigenin) and detected with specific antibodies, both coupled to AP and using two substrates, leading to differently colored products. This in situ hybridization scheme allows the simultaneous detection of two mRNA species in a tissue or cell preparation. C Amplification systems involving more than one antibody can be used to increase specificity and signal intensity.

The bottom-up synthesis of metallic nanowires was further applied to construct a nanotransistor device.93 The sequence-specific winding of the homologous nucleic acid carried by the RecA-protein into the duplex DNA was used to address the nucleic acid/protein complex on the DNA scaffold (Fig. 12.27). The subsequent association of the anti-RecA antibody to the protein DNA complex, followed by the association of the biotinylated antiantibody, and the linkage of streptavidin-modified carbon nanotube deposited the tubes in the specific domain of the DNA scaffold. The further... 

M24. Munns, T. W., Liszewski, M. K., and Hahn, B. H., Antibody-nucleic acid complexes. Conformational and base associated with spontaneously occurring poly- and monoclonal anti-DNA antibodies from autoimmune mice. Biochemistry 23, 2964-2970 (1984). 

Peptide nucleic acids (PNA) are novel antisense oligonucleotides (see Section 1.6.2) which contain a polypeptide backbone. Receptor-mediated transcytosis can be exploited to promote their delivery to the CNS. For example, the attachment of PNAs to the anti-transferrin (0X26) receptor antibodies has been shown to increase the brain uptake of the PNAs, without loss of the ability of the PNAs to hybridize to target mRNA. However, antisense agents will not exert pharmacologic effects in vivo following delivery to... 

Giovannoni, L. Viti, F. Zardi, L. Neri, D., Isolation of anti-angiogenesis antibodies from a large combinatorial repertoire by colony filter screening, Nucleic Acids Res. 2001, 29, E27... 

In time-resolved fluorescence (TRF) (Maundrell et al., 1985), europium chelates are excited at 340 nm to emit two types of fluorescence, a shortlived background fluorescence (< 0.1 ms) and a fluorescence due to emitted photons of Eu " lasting up to over 1 ms. This difference in fluorescence decay rate can be exploited by measuring fluorescence only after background fluorescence has completely decayed to obtain a very high signal to noise ratio (detectability down to 10 5 M) as shown in Fig. 7.5. Originally, anti-hapten antibody was labeled with Eu " but in more recent procedures Eu " is directly attached to the nucleic acid (Sections 7.3.2.1 and 7.8.1). 

Good assay reproducibility and recovery were observed for neat (undiluted) normal human serum and serum from rheumatoid arthritis patients for quantitation of a fully human anti-TNF-a monoclonal antibody [86]. It has also been reported that excess therapeutic antibodies present in serum were tolerated better in an assay for the detection of antitherapeutic antibodies based on the MSD ECL device [91]. Furthermore, the ECL procedure has been reported to be stable over a broad range of magnetic bead concentrations, probe concentrations, and hybridization conditions for a nucleic acid binding assay, making these assays more versatile and easier to transfer from one laboratory to another [88]. 

Pre-immunization of bone marrow transplant donors with BRC/ABL p210 protein. In patients with BCR/ABL leukemia cells, anti-leukemia cell reactive antibodies and immune T cells are generated (too weak to induce remission). Bone marrow donors pre-immunized with p210 protein (nucleic acid-free) would provide not only rescue for hematopoiesis, but antibodies co-acting with patient s NK cells, and immune T cells both cytolytic to BRC/ABL leukemia cells. Proposals are not known to have had acted upon at NCI at MD Anderson. ... 

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