Protein biochip array technology to monitor rituximab in rheumatoid arthritis.
In rheumatoid arthritis (RA) there are currently no good indicators to predict a clinical response to rituximab. The purpose of this study was to monitor and determine the role of peripheral blood cytokine profiling in differentiating between a good versus poor response to rituximab in RA. Blood samples were collected at baseline and at 3 months from 46 RA patients who were treated with rituximab. Responders are defined by the presence of three of four American College of Rheumatology criteria: >or=20% decrease in C-reactive protein, visual analogical score of disease activity, erythrocyte sedimentation rate and improvement of the disease activity score (28) (four values) by >or=1.2 obtained at 3 months. Twelve cytokines were measured from serum collected on days 0 and 90 by proteomic array, including interleukin-6 (IL-6), tumour necrosis factor-alpha, IL-1a, IL-1b, IL-2, IL-8, interferon-gamma, IL-4, IL-10, monocyte chemoattractant protein-1, epidermal growth factor and vascular growth factor. We showed that C-reactive protein and IL-6 levels decrease significantly at 3 months in the responder group compared with baseline. At day 90 we identified a cytokine profile which differentiates responders and non-responders. High serum levels of two proinflammatory cytokines, monocyte chemoattractant protein-1 and epidermal growth factor, were significantly higher in the responder group at day 90 compared with non-responders. However, we were not able to identify a baseline cytokine profile predictive of a good response at 3 months. These findings suggest that cytokine profiling by proteomic analysis may be a promising tool for monitoring rituximab and may help in the future to identify responder RA patients.
Fabre
S
S
Immuno-rheumatology, Lapeyronie University Hospital, Montpellier, France. s-fabre@chu-montpellier.fr
Guisset
C
C
Tatem
L
L
Dossat
N
N
Dupuy
A M
AM
Cohen
J D
JD
Cristol
J P
JP
Daures
J P
JP
Jorgensen
C
C
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004815:Epidermal Growth Factor / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D016015:Logistic Models; D008875:Middle Aged; D040081:Protein Array Analysis; D000069283:Rituximab; D012720:Severity of Illness Index; D013997:Time Factors; D017211:Treatment Failure
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D000069283:Rituximab; D004815:Epidermal Growth Factor; D002097:C-Reactive Protein