DOI Seite / Zitierlink:
https://doi.org/10.11588/diglit.48120#0068
50 Molecular and Cell Biology of Autoantibodies and Autoimmunity
been detected are antibodies against isoleucyl- and glycyl-tRNA-synthetases, and
antibodies against a moiety that is believed to be the protein synthesis elongation
factor-1 (EF-1). Interestingly, patient's sera often contain more than one tpye of
antibody, but no serum has yet been reported in which low or more of the tRNA
related specificities coexist.
A New Autoantibody Specific for the Limited Systemic Sclerosis (ISSc)
Found Through Molecular Biology
G. G. Maul, P. McGregory, D. Ziemnicka-Kotula, and C. Ascoli
The Wistar Institute of Anatomy and Biology, 36th Street at Spruce, Philadelphia,
PA 19104, USA
Presently there are two relatively specific autoantibody systems recognized for
systemic sclerosis (SSc). About 35% of patient sera with diffuse SSc recognize
topoisomerase I and about 65% of ISSc recognize one or more of the three low-
abundance proteins of the kinetochore. Proteins that are rare and present in struc-
tures similarly appearing in immunofluorescence will not be recognized by double
immunodiffusion or immunoblotting. They may, however, be found through
cloning.
During our attempts to clone the 140 kDa protein of the kinetochore we
selected a clone recognized by several sera from ISSc patients. To determine the
antigenic localization of the protein cloned we produced monoclonal antibodies
against the fusion protein. The monoclonal antibody did not recognize the
kinetochore. Instead it labeled new nuclear domain consisting of 8- 16 variously
sized precisely circumscribed dots. Double labeling proved that the antigen
localization was not on the prekinetochore nor was it on the primary constriciton
of chromosomes. The protein is translated from a 100 kDa in RNA and partial
sequencing shows that it does not correspond to any known protein.
Immunohistochemical ultrastructural analysis lends credence to the observa-
tion that some of these dots appear as rings or hollow spheres, are present as pairs
and may double during the cell cycle. Together with observations from other sera
recognizing the same structure we conclude that we have cloned the first protein
of a new nuclear domain for which a function has yet to be found.
Large scale screening showed that the new antibodies are ISSc-specific (65%
of patients), that the kinetochore antibodies of SLE patients do not react with
this antigen, that the sera of primary biliary cirrhosis patients are negative unless
been detected are antibodies against isoleucyl- and glycyl-tRNA-synthetases, and
antibodies against a moiety that is believed to be the protein synthesis elongation
factor-1 (EF-1). Interestingly, patient's sera often contain more than one tpye of
antibody, but no serum has yet been reported in which low or more of the tRNA
related specificities coexist.
A New Autoantibody Specific for the Limited Systemic Sclerosis (ISSc)
Found Through Molecular Biology
G. G. Maul, P. McGregory, D. Ziemnicka-Kotula, and C. Ascoli
The Wistar Institute of Anatomy and Biology, 36th Street at Spruce, Philadelphia,
PA 19104, USA
Presently there are two relatively specific autoantibody systems recognized for
systemic sclerosis (SSc). About 35% of patient sera with diffuse SSc recognize
topoisomerase I and about 65% of ISSc recognize one or more of the three low-
abundance proteins of the kinetochore. Proteins that are rare and present in struc-
tures similarly appearing in immunofluorescence will not be recognized by double
immunodiffusion or immunoblotting. They may, however, be found through
cloning.
During our attempts to clone the 140 kDa protein of the kinetochore we
selected a clone recognized by several sera from ISSc patients. To determine the
antigenic localization of the protein cloned we produced monoclonal antibodies
against the fusion protein. The monoclonal antibody did not recognize the
kinetochore. Instead it labeled new nuclear domain consisting of 8- 16 variously
sized precisely circumscribed dots. Double labeling proved that the antigen
localization was not on the prekinetochore nor was it on the primary constriciton
of chromosomes. The protein is translated from a 100 kDa in RNA and partial
sequencing shows that it does not correspond to any known protein.
Immunohistochemical ultrastructural analysis lends credence to the observa-
tion that some of these dots appear as rings or hollow spheres, are present as pairs
and may double during the cell cycle. Together with observations from other sera
recognizing the same structure we conclude that we have cloned the first protein
of a new nuclear domain for which a function has yet to be found.
Large scale screening showed that the new antibodies are ISSc-specific (65%
of patients), that the kinetochore antibodies of SLE patients do not react with
this antigen, that the sera of primary biliary cirrhosis patients are negative unless