Background:
A disintegrin and metalloproteinase
(ADAM) 10 has been reported to be involved in certain autoimmune diseases, such
as rheumatoid arthritis. In this study, we demonstrate that ADAM10, which is a
member of the ADAM family, is expressed in angiitis, and we examine its
relationship to this condition using clinical data.
Materials
and Methods: The ADAM10 levels in
serum from microscopic polyangiitis (MPA) patients and healthy controls were
measured using enzyme-linked immunosorbent assay. The clinical data were
collected from Showa University cohort data. The relationship between the
ADAM10 level in the sera and the clinical data was evaluated using Spearman’s rank
correlation.
Results:
No significant differences were
observed in the mean age or gender ratio between the MPA patients and the
healthy controls. The ADAM10 level in MPA serum (n=10) was significantly
elevated compared with that in healthy control serum (n=7) (450 ± 44 pg/ml and
85 ± 33 pg/ml, respectively). The ADAM10 level in MPA serum was also
significantly negatively correlated with myeloperoxidase anti-neutrophil
cytoplasmic antibody (MPO-ANCA) titer, but not with the C-reactive protein
level.
Discussion: ADAM10 is elevated in
MPA patients and might be involved in their inflammation. On the other hand,
ADAM10 is negatively correlated with MPO-ANCA. These results indicate that
ADAM10 might be involved in inflammation other than MPO-ANCA.
A disintegrin and metalloproteinases
(ADAMs) are a family of proteinases that are known to be involved in ectodomain
cleavage and in the regulation of the intramembrane proteolysis of transmembrane
proteins. ADAM10 and 17 are the major proteases that cleave some membrane-bound
proteins, and have extensive overlap with and compensate for several
substrates, including epidermal growth factor receptor ligands, tumor necrosis
factor (TNF), TNF receptor, and interleukin (IL)-6 receptor. ADAM17 is
also known as TNF-α converting enzyme (TACE) and was identified as the primary
protease responsible for the proteolytic processing of TNF-α. ADAM17 is
expressed in numerous human tumors and is associated with invasion and
metastasis. ADAM10 is also involved in the shedding of many substrates
that play roles in cancer progression, allergic responses and inflammatory
diseases. We previously showed that ADAM10 is involved in angiogenesis
and the inflammation associated with rheumatoid arthritis (RA). However,
the role of ADAM10 in other autoimmune diseases has not been examined. Here, we
describe the expression and possible implications of ADAM10 in angiitis.
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