Clues to pathogenesis of spondyloarthropathy derived from synovial fluid mononuclear cell gene expression profiles.
OBJECTIVE
To use gene expression profiles of spondyloarthropathy (SpA) synovial fluid mononuclear cells (SFMC) to determine if there are transcripts that support the unfolded protein response (UPR) hypothesis, and to identify which cytokines/chemokines are being expressed and which cell fractions are involved.


METHODS
Gene expression profiles were generated by microarray screening of SFMC of 5 patients with SpA, 5 patients with rheumatoid arthritis (RA), and peripheral blood mononuclear cells (PBMC) of 6 controls. Results were validated by reverse transcription polymerase chain reaction using samples from a larger panel of subjects.


RESULTS
The repertoires of proinflammatory cytokines/chemokines expressed by SpA and RA SFMC were very similar: monocyte chemotractant protein 1 (MCP-1), interleukin 8 (IL-8), IL-1beta, endothelial-monocyte activating polypeptide II, interferon-gamma, and tumor necrosis factor-alpha. MCP-1 was highly expressed in SpA SFMC. There was enhanced expression of immunoglobulin heavy chain binding protein (BiP) in SpA, which is compatible with the UPR hypothesis. BiP was most highly expressed in the adherent fraction of SpA SFMC.


CONCLUSIONS
Previous data postulating UPR in SpA are based on in vitro experiments with transfected cell lines. Our patient derived data suggest that it also occurs in vivo in the macrophages of SpA joints.
Gu
Jieruo
J
University of California Los Angeles, 90095, USA.
Rihl
Markus
M
Märker-Hermann
Elisabeth
E
Baeten
Dominique
D
Kuipers
Jens G
JG
Song
Yeong Wook
YW
Maksymowych
Walter P
WP
Burgos-Vargas
Ruben
R
Veys
Eric M
EM
De Keyser
Filip
F
Deister
Helmuth
H
Xiong
Momiao
M
Huang
Feng
F
Tsai
Wen Chan
WC
Yu
David Tak Yan
DT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005820:Genetic Testing; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025242:Spondylarthropathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*
D018925:Chemokines