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,a
Ch Meier,b
H W Vohr,c
M Schwochau,b
Ch Specker,d
G R Burmestera
a Department of Medicine III, Rheumatology
and Clinical Immunology, Charité University Hospital, Humboldt
University of Berlin, Germany, b Institute for Genetics, Heinrich Heine University of
Düsseldorf, Germany, c Institute for Toxicology, Pharmacological Research Centre
Aprath, Bayer AG, Wuppertal, Germany, d Department of Rheumatology, University Clinics of
Düsseldorf, Germany
Correspondence to: Dr S Blä, Immunologisch-Rheumatologisches Labor,
Charité, Tucholskystr 2, D-10117 Berlin, Germany.
Accepted for publication 4 February 1998
OBJECTIVE
The autoantigen p68 is a target of
autoantibodies as well as autoreactive T cells with a high specificity
in rheumatoid arthritis (RA). The binding characteristics of the
autoantibodies to their antigen were now analysed biochemically and cytologically.
METHODSDeglycosylation techniques as well as
lectin and sugar competition experiments were performed to p68 to
discover if the antibodies detected a glycoepitope. Its antigenicity
was investigated applying anti-p68 antibodies derived from RA patients
in comparison with polyclonal rabbit anti-p68 antibodies.
RESULTSp68 specific antibodies from RA patients
did not to bind to p68 that had been deglycosylated by alkaline
-elimination, O-glycosidase or periodate treatment.
In contrast, binding of p68 specific antibodies raised in rabbit was
unaffected by either deglycosylation protocol. Furthermore, lectins
specific for the carbohydrate N-acetylglucosamine competed
with p68 specific antibodies from RA patients for antigen binding.
N-acetylglucosamine by itself also competed with patient derived anti-p68 antibodies for p68 binding. Again, rabbit anti-p68 antibodies did not elicit these competitive effects. Applying cytoimmunofluorescence, p68 was present in the cytoplasm or endoplasmic reticulum and also in low abundance on the cell surface. Under heatshock conditions, p68 was detectable in the nucleus.
CONCLUSIONSAutoimmunity to p68 during RA is
carried by anti-carbohydrate autoantibodies. The carbohydrate
modification of p68 appears to be N-acetylglucosamine,
which may reflect the regulation of intracellular localisation of the
antigen. It is hypothesised that a shift in glycosylation pattern
accompanied by an unphysiological localisation of the antigen could
trigger antigenicity of p68 during the pathogenesis of RA.
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