狼瘡病人血清中抗中性白血球抗體的免疫活性,對應抗原的鑑定,及臨床應用(3/3)
Date Issued
2004-12-02
Date
2004-12-02
Author(s)
余家利
DOI
922314B002115
Abstract
Leukopenia is a quite common hematological abnormality found in patients
with systemic lupus erythematosus (SLE). It had been reported that the
prevalence rate of anti-polymorphonuclear neutrophil antibodies (anti-PMN)
is found in 50-60% of SLE sera in parallel with lupus activity. By using
cellular ELISA of normal PMN as substrate, we demonstrated that the anti-PMN
activity in SLE sera is significantly higher than normal sera. In addition,
the anti-PMN activity of SLE-sera may elicit PMN apoptosis as detected by
flow cytometry. Furthermore, the binding of SLE anti-PMN autoantibodies
enhanced phagocytic activity and IL-8 production by normal PMN. These
results render us to conclude that neutropenia in SLE is caused by the
presence of anti-PMN in the sera that cytotoxic to PMN via the mechanism
of activation induced cell death (AICO), To identify the cognate antigen(s)
of anti-PMN autoantibodies on the PMN surface,Western blot analysis of
biotinylated normal PMN lysates previously immunoprecipitated by either
normal or SLE sera and were then probed by HRP-avidin and. We found that
the 47-50kDa membrane molecule was the cognate antigen of SLE anti-PMN.
Proteomics study revealed the ≒50kDa protein was 99.5% homologous with
human nuclear SSB/La molecule. Molecular cloning of the gene-encoding SSB/La
was obtained from human derived leukocyte cDNA library. After insertion,
proliferation, induction and expression of the SSB/La encoding gene, the
expressed protein was further purified by His-tag column. Using affinity
column of SSB/La-Sepharose column, human polyclonal anti-SSB/La
autoantibodies were partially purified from SLE sera containing high
anti-SSB/La activity. The anti-SSB/La autoantibodies were proved to be
cytotoxic to normal human PMN. Interestingly, both anti-SSB/La autoantibodies
and SSB/La protein exhibited PMN activation effects including
phagocytosis and IL-8 production as mentioned in the above paragraph.
However, the addition of SSB/La and anti-SSB/La antibodies did not increase
these activation. These results suggest that SSB/La protein may probably
act as a “danger signal” to the innate immune system in that release of SSB/La
molecules from the injured cell alert the phagocytes to activation. However,
further investigations are needed to clarifty this observation.
Subjects
lecukopenia
anti-neutrophil antibodies
systemic lupus erythematosus
SSB/La protein
apoptosis
activation-induced cell death
death signal
Publisher
臺北市：國立臺灣大學醫學院分子醫學研究所
Type
journal article
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