DOI Page / Citation link:
https://doi.org/10.11588/diglit.48120#0127
Abstracts
109
ing domains, by enzymatic digestion of the protein. All sera with autoantibodies
to poly(ADP-ribose) polymerase recognized the NAD-binding domain of the en-
zyme, as demonstrated by either immunoblotting or immunoprecipitation ex-
periments of partially proteolyzed poly(ADP-ribose) polymerase. The autoan-
tibodies also inhibited the catalytic activity of the purified calf enzyme, as mea-
sured by the transfer of ADP-ribose from [32P]NAD to either histones or to po-
ly(ADP-ribose) polymerase itself.
Because comparative structural analyses have shown that the active sites of en-
zymes are often conserved during evolution, we tested the ability of the autoan-
tibodies to react with poly(ADP-ribose) polymerase from lower eukaryotes. The
human autoantibodies react with poly(ADP-ribose) polymerase in cellular extract
from mammalian, avian, amphibian, arthropod, and protozoan cells, and also in-
hibit the catalytic activity of the various enzymes. Furthermore, the analysis of
the cDNA of poly(ADP-ribose) polymerase revealed that an autoantigenic frag-
ment of this protein is reminiscent of other NAD-utilizing dehydrogenases in the
predicted secondary structure. These experiments indicate that the human au-
toantibodies to poly(ADP-ribose) polymerase recognize a distinctive group of
evolutionarily conserved antigenic determinants that are closely related to the
catalytic site of the enzyme. The results are consistent with the hypothesis that the
epitope selectivity of human autoantibodies to poly(ADP-ribose) polymerase is
influenced by cross-reactive antigens in the external environment.
Rheumatoid Arthritis is Associated with the Presence of Anti-Nuclear
Antibodies to A 33 kD Protein (RA33) and Related Antigens
W. Hassfeld, G. Steiner, and J. S. Smolen
2nd Department of Medicine, University of Vienna, and 2nd Department of Medicine -
Center for Rheumatic Diseases, Lainz Hospital, Vienna, Austria
Autoantibodies to nuclear antigens (ANA) represent hallmarks of several in-
flammatory rheumatic diseases. Particular ANA-subsets are characteristic for cer-
tain disorders, such as anti-Sm for systemic lupus erythematosus, anti-Scl 70 for
scleroderma, and anti-SSB for primary Sjogrenjs syndrome. In contrast to these
“connective tissue diseases”, rheumatoid arthritis (RA) has not been associated
with antibodies to nuclear antigens, nor is there a pathogenomic autoantibody
known for this disorder. In the present investigation we have analysed sera from
patients with RA for the presence of antibodies to nuclear proteins. To this end,
109
ing domains, by enzymatic digestion of the protein. All sera with autoantibodies
to poly(ADP-ribose) polymerase recognized the NAD-binding domain of the en-
zyme, as demonstrated by either immunoblotting or immunoprecipitation ex-
periments of partially proteolyzed poly(ADP-ribose) polymerase. The autoan-
tibodies also inhibited the catalytic activity of the purified calf enzyme, as mea-
sured by the transfer of ADP-ribose from [32P]NAD to either histones or to po-
ly(ADP-ribose) polymerase itself.
Because comparative structural analyses have shown that the active sites of en-
zymes are often conserved during evolution, we tested the ability of the autoan-
tibodies to react with poly(ADP-ribose) polymerase from lower eukaryotes. The
human autoantibodies react with poly(ADP-ribose) polymerase in cellular extract
from mammalian, avian, amphibian, arthropod, and protozoan cells, and also in-
hibit the catalytic activity of the various enzymes. Furthermore, the analysis of
the cDNA of poly(ADP-ribose) polymerase revealed that an autoantigenic frag-
ment of this protein is reminiscent of other NAD-utilizing dehydrogenases in the
predicted secondary structure. These experiments indicate that the human au-
toantibodies to poly(ADP-ribose) polymerase recognize a distinctive group of
evolutionarily conserved antigenic determinants that are closely related to the
catalytic site of the enzyme. The results are consistent with the hypothesis that the
epitope selectivity of human autoantibodies to poly(ADP-ribose) polymerase is
influenced by cross-reactive antigens in the external environment.
Rheumatoid Arthritis is Associated with the Presence of Anti-Nuclear
Antibodies to A 33 kD Protein (RA33) and Related Antigens
W. Hassfeld, G. Steiner, and J. S. Smolen
2nd Department of Medicine, University of Vienna, and 2nd Department of Medicine -
Center for Rheumatic Diseases, Lainz Hospital, Vienna, Austria
Autoantibodies to nuclear antigens (ANA) represent hallmarks of several in-
flammatory rheumatic diseases. Particular ANA-subsets are characteristic for cer-
tain disorders, such as anti-Sm for systemic lupus erythematosus, anti-Scl 70 for
scleroderma, and anti-SSB for primary Sjogrenjs syndrome. In contrast to these
“connective tissue diseases”, rheumatoid arthritis (RA) has not been associated
with antibodies to nuclear antigens, nor is there a pathogenomic autoantibody
known for this disorder. In the present investigation we have analysed sera from
patients with RA for the presence of antibodies to nuclear proteins. To this end,