Blood chemokine profile in untreated early rheumatoid arthritis: CXCL10 as a disease activity marker.
BACKGROUND
We have recently analyzed the profile of T-cell subtypes based on chemokine receptor expression in blood from untreated early rheumatoid arthritis (ueRA) patients compared to healthy controls (HC). Here, we compared the levels of the respective chemokines in blood plasma of ueRA patients with those of HC. We also studied the association of chemokine levels with the proportions of circulating T-cell subsets and the clinical disease activity.


METHODS
Peripheral blood was obtained from 43 patients with ueRA satisfying the ACR 2010 criteria and who had not received any disease-modifying anti-rheumatic drugs (DMARD) or prednisolone, and from 14 sex- and age-matched HC. Proportions of T helper cells in blood, including Th0, Th1, Th2, Th17, Th1Th17, TFh, and regulatory T cells, were defined by flow cytometry. Fifteen chemokines, including several CXCL and CCL chemokines related to the T-cell subtypes as well as to other major immune cells, were measured in blood plasma using flow cytometry bead-based immunoassay or ELISA. Clinical disease activity in patients was evaluated by assessing the following parameters: Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), swollen joint counts (SJC), tender joint counts (TJC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The data were analyzed using multivariate factor analyses followed by univariate analyses.


RESULTS
Multivariate discriminant analysis showed that patients with ueRA were separated from HC based on the blood plasma chemokine profile. The best discriminators were CXCL9, CXCL10, CXCL13, CCL4, and CCL22, which were significantly higher in ueRA compared to HC in univariate analyses. Among the chemokines analyzed, only CXCL10 correlated with multiple disease activity measures, including DAS28-CRP, DAS28-ESR, CDAI, SJC in 66 joints, CRP, and ESR.


CONCLUSIONS
High circulating levels of CXCL10 in the plasma of ueRA patients and the association with the clinical disease activity suggests that CXCL10 may serve as a disease activity marker in early rheumatoid arthritis.
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden. Jayesh.Pandya@rheuma.gu.se.
Jayesh M
JM
Pandya
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden.
Anna-Carin
AC
Lundell
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden.
Kerstin
K
Andersson
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden.
Inger
I
Nordström
Department of Rheumatology, Skåne University Hospital Lund and Malmö, Lund University, Lund, Sweden.
Elke
E
Theander
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden. Anna.Rudin@microbio.gu.se.
Anna
A
Rudin
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000097:blood*; D018925:Chemokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D054357:Chemokine CXCL10; D018925:Chemokines; D002097:C-Reactive Protein
CXCL10; Chemokine; Chemokine receptor; Multivariate discriminant analysis; Rheumatoid arthritis; T cell