High concentration of soluble HLA-DR in the synovial fluid: generation and significance in "rheumatoid-like" inflammatory joint diseases.
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.
Claus
R
R
Institute of Immunology, University Rostock, Germany. renate.claus@med.uni-rostock.de
Bittorf
T
T
Walzel
H
H
Brock
J
J
Uhde
R
R
Meiske
D
D
Schulz
U
U
Hobusch
D
D
Schumacher
K
K
Witt
M
M
Bartel
F
F
Hausmann
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000276:immunology; D015703:Antigens, CD / Q000097:blood / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000097:blood / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012995:Solubility; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger