DNA, anti-native, antibodies

Grennan DM, Sturrock (1976) Polyarthritis, hepatitis and anti-native DNA antibodies after treatment with ethambutol and rifampicin. Tubercle 57 259... 

Anti-native DNA antibodies and anti-ribonucle-ase resistant Sm antibodies are usually uncommon in MCTD and are associated with a severe flare-up of lupus-like features. 

The anti-native DNA antibodies react equally well with DNAs which differ in their composition (DNA from mammalian cells, bacteria or virus) and thus it is unlikely that base sequence determinants are recognized, and specificity is essentially conformation-dependent. Antibodies reacting with native DNA have been described in several other human diseases (Koffler et al., 1969 Monier et al., 1970). However, the level was very low and their specificity has not been studied. 

Steinberg et al. (1969) have shown the existence of antibodies binding specifically with poly rl-poly rC labelled with in the sera of NZB and NZB/W mice as well as in the sera of SLE patients. This reaction can be inhibited by double-helical polyribonucleotide complexes. They showed also that these antibodies are different from anti-native DNA antibodies because the latter are not inhibited by double-helical polyribonucleotides. They later confirmed these results (Talal et al., 197I) by studies of reciprocal inhibition... 

A6. Alarcon-Segovia, D., and Llorente, L., Antibody penetration into living cells. IV. Different effects of anti-native DNA and anti-ribonucleoprotein IgG on the cell cycle of activated T gamma cells. Clin. Exp. Immunol. 52, 365-371 (1983). 

A high titer of antinuclear antibodies and antidouble-stranded native DNA antibodies occurred during treatment with pyritinol 400 mg/day in a woman with rheumatoid arthritis (11). A clear temporal relation and a reduction in antinuclear antibody titers and disappearance of anti-DNA antibodies after drug withdrawal strongly suggested a causal relation. 

In summary, structural analyses of anti-DNA antibodies support the hypothesis that autoimmunity to DNA is both initiated and sustained as a clonally selected, antigen-specific immune response to DNA. The initial autoimmune response to DNA is dominated by lower affinity IgM antibody primarily specific for single-stranded, denatured mammalian DNA. As the autoimmune response progresses, the antibody isotype switches to IgG, and the antibody acquires increasing affinity for native, double-stranded DNA. 

Narrower specificities have been obtained with antibodies to some unusual helical structures. Poly(dG)-poly(dC) induces antibodies specific for the immunogen and unreactive with other deoxyribonucleotide polymers, such as poly(dAT) or native DNA. Double-helical polyribonucleotides with modified furanoses, such as poly(A)-poly(2 -0-methylU), induce antibodies that react with a number of polymers bearing 2 -furanose substitutions (such as methyl or ethyl groups on either the purine or pyrimidine-containing strand). Poly(G)-poly(C) induced antibodies of narrow specificity in our studies, but Lacour and co-workers obtained anti-poly(G)-poly(C) that cross-reacted with several forms of viral RNA. ... 

Anti-DNA antibodies Usually present (native DNA) Only to single-stranded DNA... 

Thrombocytopenia—fewer than 100,000/mm in the absence of offending drugs Anti-DNA antibody to native DNA in abnormal titer... 

With the exception of antibodies reacting only with native DNA all the different kinds of anti-polynucleotide antibodies described above can be induced experimentally. 

Schwartz and Stollar (1969) and Stollar (1970) observed no reaction with either native or denatured DNA. The reaction with DNA observed with certain anti-poly A poly U (equimolar ratio) sera by Nahon et al. (1967 b) and by Lacour et al. (1968) could be due to the presence of anti-poly A antibodies in these immune sera. 

Experimentally, anti-dsDNA antibodies have been successfully induced by a complex of native calf thymus DNA and a highly immunogenic DNA-binding peptide Fusl (D7). 

Although the anti-poly G poly C sera react with poly dG poly dC, no precipitation with Micrococcus lysodeikticus DNA (72% GC) is observed, whether native or heat-denatured DNA is used. Negative results are also obtained with native or denatured DNA from E, coli, Clostridium j>erfringens, phage 2 C, chicken myeloblastic leukemic cells or calf thymus. In contrast, antibodies to poly G poly C react with RNA and appear to be capable of distinguishing ribonucleic acids according to their origin. 

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