Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritisReportar como inadecuado

Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 16:R42

First Online: 04 February 2014Received: 18 September 2013Accepted: 24 January 2014


IntroductionSpondyloarthritis SpA comprises a group of diseases often associated with HLA-B27 and characterized by inflammation of the entheses and joints of the axial skeleton. The inflammatory process in SpA is presumably driven by innate immune cells but is still poorly understood. Thus, new tools for monitoring and treating inflammation are needed. The family of CD18 integrins is pivotal in guiding leukocytes to sites of inflammation, and CD18 hypomorphic mice develop a disease resembling SpA. Previously, we demonstrated that altered soluble CD18 sCD18 complexes in the blood and synovial fluid of patients with arthritis have anti-inflammatory functions. Here, we study the mechanisms for these alterations and their association with SpA disease activity.

MethodsPlasma levels of sCD18 in a study population with 84 patients with SpA and matched healthy controls were analyzed with a time-resolved immunoflourometric assay TRIFMA. Binding of sCD18 to endothelial cells and fibroblast-like synoviocytes FLSs was studied with confocal microscopy. Shedding of CD18 from peripheral blood mononuclear cells PBMCs was studied with flow cytometry and TRIFMA.

ResultsPlasma levels of sCD18 were decreased in patients with SpA compared with healthy volunteers P <0.001, and the lowest levels were in the HLA-B27-positive subgroup P <0.05. In a multiple regression model, the sCD18 levels exhibited an inverse correlation with the Bath Ankylosing Spondylitis Disease Activity Index BASDAI P <0.05, the level of morning stiffness P <0.05, the Bath Ankylosing Spondilitis Metrology Index P <0.05, the physician global assessment score P <0.01, and the sacroiliac magnetic resonance imaging activity score P <0.05. The mechanisms for these changes could be simulated in vitro. First, sCD18 in plasma adhered to inflammation-induced intercellular adhesion molecule 1 ICAM-1 on endothelial cells and FLS, indicating increased consumption. Second, CD18 shedding from SpA PBMCs correlated inversely with the BASDAI P <0.05, suggesting insufficient generation. CD18 was shed primarily from intermediate CD14 CD16 monocytes, supporting the view that alterations in innate immunity can regulate the inflammatory processes in SpA.

ConclusionsTaken together, the failure of patients with SpA to maintain adequate sCD18 levels may reflect insufficient CD18 shedding from monocytes to counterbalance the capture of sCD18 complexes to inflammation-induced ICAM-1. This could increase the availability of ICAM-1 molecules on the endothelium and in the synovium, facilitating leukocyte migration to the entheses and joints and aggregating disease activity.

AbbreviationsBASDAIBath Ankylosing Spondylitis Disease Activity Index

BASFIBath Ankylosing Spondylitis Functional Index

BASMIBath Ankylosing Spondilitis Metrology Index

CRcomplement receptor

CRPC-reactive protein

DMEMDulbecco’s modified Eagle’s medium

FCSfetal calf serum

FITCfluorescein isothiocyanate

FLSfibroblast-like synoviocyte

HChealthy control

ICAM-1intercellular adhesion molecule 1

mAbmonoclonal antibody

MFImean fluorescence intensity

MMPmatrix metalloproteinase

MRImagnetic resonance imaging

NHSnormal human serum

NKnatural killer

PBMCperipheral blood mononuclear cell

RArheumatoid arthritis

RTroom temperature

sCD18soluble CD18

SFMCsynovial fluid mononuclear cell

SIJsacroiliac joint


TBSTris-buffered saline

Th17T helper 17

TNF-αtumor necrosis factor-alpha

TRIFMAtime-resolved immunfluorometric assay

VASvisual analogue scale.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4471 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Tue W Kragstrup - Babak Jalilian - Malene Hvid - Anders Kjærgaard - René Østgård - Berit Schiøttz-Christensen - Anne 


Documentos relacionados