Abstract
Background
Inflammation and chemokines play a pivotal role in aseptic loosening (AL) and prosthetic joint infection (PJI) of total joint arthroplasty (TJA). Recently, the Duffy antigen receptor for chemokines (DARC) on erythrocytes was identified as a potent chemokine receptor able to bind and carry without deactivating a wide range of CXC and CC chemokines from circulation to tissues. The role of DARC and its functional polymorphism (SNP) influencing the number of the DARC molecules on the erythrocytes in AL/PJI has not been studied yet.
Methods
We genotyped functional polymorphism in the DARC gene (rs12075) using MassArray technology (Agena Bioscience) in 354 patients with TJA (hip and knee arthroplasties). Patients were further subdivided into those with a complication (AL, n = 110; PJI, n = 126) and a control group without complications for at least 10 years (n = 118). Statistics was performed by Plink 1.07 and relative entropy.
Results
Among our TJA patients, the rs12075 *G allele was more frequent in patients with a failure (46.6%) compared to those without complications (36.0%, P = 0.007, OR = 1.55, 95%CI = 1.13–2.14). The rs12075 *G allele was overrepresented mainly in patients with AL (49.5%, P = 0.004, OR = 1.74, 95%CI = 1.20–2.54), a trend was observed in PJI (44.0%, P = 0.071, OR =1.40, 95%CI = 0.97–2.01). This SNP is located in a coding region in the DARC gene, and the *G allele is associated with more DARC molecules on erythrocytes, thus able to bind and transport more CCL2, CCL5, CCL18 involved in the pathogenesis of AL/PJI from circulation to the periprosthetic tissue.
Conclusions
Our data nominate erythrocyte DARC as a novel molecule in pathogenesis of aseptic loosening of TJA. The hypothesis that DARC may serve as a chemokine reservoir and shuttle chemokines from circulation to the joint surroundings should be investigated in future studies.
Level of evidence IV
Evidence from well-designed case-control and cohort studies.
The study was approved by the Ethical Committee of Palacky University and Faculty.
