Correlation of CX3CL1 and CX3CR1 levels with response to infliximab therapy in patients with rheumatoid arthritis.
OBJECTIVE
To examine the relation between serum chemokine levels and patient responsiveness to infliximab, and the influence of infliximab administration on serum chemokine levels.


METHODS
Serum levels of the chemokines CX3CL1, CXCL8, CCL3, and CXCL10 were quantified prior to (at baseline) and after 30 weeks of treatment with infliximab in 20 patients using enzyme-linked immunosorbent assays. Disease status was assessed using the Disease Activity Score (DAS28). The response to infliximab was classified according to the European League Against Rheumatism (EULAR) response criteria.


RESULTS
By 30 weeks, infliximab produced a significant overall reduction in DAS28 among the 20 patients with RA, although only 12 achieved a good to moderate response based on EULAR response criteria. A significant reduction in CX3CL1 was seen in the responsive group, although infliximab treatment had no significant effect on the serum levels of the other 3 chemokines. Comparison of patients with lower (<2000 pg/ml) and higher (>or=2000 pg/ml) basal CX3CL1 levels revealed that DAS28, erythrocyte sedimentation rate, C-reactive protein, and CX3CL1 levels were all significantly diminished by infliximab in RA patients with lower basal CX3CL1 levels, but not in those with higher basal levels. In addition, cell-surface expression of CX3CR1 protein in peripheral blood CD8+CD3+ T cells and mRNA expression of CX3CR1 in lymphocytes were both significantly downregulated after infliximab treatment in the responsive group.


CONCLUSIONS
Our results suggest that the CX3CL1-CX3CR1 system in patients with active RA may be sensitive to anti-tumor necrosis factor-alpha therapy, and confirm that CX3CL1 plays a crucial role in the pathogenesis of RA.
Division of Rheumatology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, 142-8666, Japan.
Tsuyoshi
T
Odai
Mizuho
M
Matsunawa
Ryo
R
Takahashi
Kuninobu
K
Wakabayashi
Takeo
T
Isozaki
Nobuyuki
N
Yajima
Yusuke
Y
Miwa
Tsuyoshi
T
Kasama
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000097:blood*; D004185:Disability Evaluation; D005260:Female; D006304:Health Status; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000097:blood*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine; D000069285:Infliximab