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High concentration of soluble HLA-DR in the synovial fluid: Generation and significance in rheumatoid-like inflammatory joint diseases
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DOI：10.1006/cimm.2000.1729.png)
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Abstract
En 中文
In the search for its role in inflammatory joint diseases, soluble HLA-DR (sHLA-DR) was quantitated in 72 synovial fluids (SF) by a newly established immunoenzyme assay. Unlike other soluble receptors which accumulated only moderately (sCD25, sCD4) or negligibly (sHLA class I, sCD8) in the SF, SF sHLA-DR levels exceeded serum levels by up to 3 orders of magnitude and varied disease dependently from control values (traumatic synovitis and osteoarthritis: 9.9 +/- 6.1 ng/ml), Clear-cut different SF sHLA-DR values in HLA-DR-associated rheumatoid-like (136.5 +/- 130.0 ng/ml) vs HLA-B27-associated spondylarthropathy-like arthritic forms (28.4 +/- 29.1 ng/ml) were most significant comparing oligoarticular juvenile chronic arthritis type I (147.6 +/- 112.6 ng/ml) and type II (3.3 +/- 1.1 ng/ml), thus offering a new classification marker. Also ex vivo large amounts of sHLA-DR were released spontaneously by SF mononuclear cells and found to be related to the T-cell activation state. SF sHLA-DR may be shed in large complexes or micelles, as it eluted mainly at >450 kDa on gel filtration, Western blotting revealed that the majority of SF sHLA-DR consisted of full-length alpha- and beta -chains. Minor fractions of smaller sized antigens seemed to be generated by proteolytic cleavage rather than by alternative splicing, since only minute amounts of HLA-DRB mRNA lacking the transmembrane exon could be amplified by RT-PCR. Distinct forms of high-dose sHLA-DR, able to provoke rather than to suppress T-cell responses, are discussed as contributing to some HLA-DR disease association, (C) 2000 Academic Press.
Keywords:
rheumatoid arthritis
juvenile chronic arthritis
synovial fluid
soluble HLA-DR
soluble HLA class I
soluble IL-2R
soluble CD4
soluble CD8
T-lymphocyte activation
alternative splicing
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