Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Elevated Levels of CXCL9 or CXCL10 in Sera of Patients with Early RA Predict Greater Difficulty in Achieving Remission during the First Year of Treatment.

Emkey5,  Gregory R., Strle6,  Klemen, Antolini3,  Christopher R., Collier5,  Deborah S., Seton5,  Margaret, Khosroshahi5,  Arezou, Fisher2,  Mark

Massachusetts General Hospital, Sudbury, MA
Massachusetts General Hospital, Haddon Heights, NJ
Massachusetts General Hospital, Denver, CO
Massachusetts General Hospital, Charlestown, MA
Massachusetts General Hospital, Boston, MA
Massachusetts General Hospital

Purpose:

The inflammatory immune response in patients with early rheumatoid arthritis (RA) is not well characterized. Depending on the series, dominant Th1-, Th2-, or Th17-type immune responses have been reported. We hypothesized that cytokine and chemokine levels, which act as indicators of these types of responses, may serve as biomarkers to help stratify subgroups of RA patients and predict their disease course. Here we report a preliminary analysis of a prospective study evaluating immune responses in early RA patients.

Methods:

Patients who met EULAR criteria for RA, had symptoms for <12 months, and had not yet received DMARD therapy, were entered into the study and followed at 3, 6, and 12 months. They were treated with DMARDs, primarily methotrexate; and with a TNF inhibitor if the response was incomplete. At each visit, clinical parameters were determined (HAQ and DAS28 [CRP]), and serum samples and synovial fluid, if available, were collected. The levels of 20 cytokines and chemokines were determined in all samples at the same time using bead-based Multiplex assays. Elevated levels of each factor were defined as >2SD above the mean value of 40 control subjects.

Results:

To date, 35 patients have been enrolled in the study; 30 patients have completed 3 months follow-up, and 12 have completed 12 months follow up. Of the 20 cytokines and chemokines measured, elevated levels of CXCL9 or CXCL10 (IFN-inducible chemoattractants for Th1 effector cells) or IL-23 (a marker for Th17 responses) were most common. In the initial visit, prior to DMARD therapy, 17 patients (49%) had elevated levels of CXCL9 or CXCL10, 17 (49%) had elevated IL-23 levels, and 26 (74%) had one or both of these responses. At study entry, patients who had elevated levels of CXCL9 or 10 had similar DAS28 scores (median, 5.2) as patients who did not have elevated levels of these chemokines (4.8). However, at the 3 month follow-up, patients with elevated levels of CXCL9 or 10 had a median DAS28 score of 3.1 compared with 2.2 in patients without elevated levels (P=0.03), and by 12 months, the 2 groups had diverged more (3.1 versus 1.25, P=0.004). Similar differences between the 2 groups were observed with HAQ scores. All 5 patients in whom it was possible to obtain joint fluid had elevated levels of both CXCL9 and 10 in serum and at least 10-fold higher levels of both chemokines in joint fluid. Elevated serum levels of IL-23 alone, without CXCL9 or 10, were not a risk factor for more severe disease.

Conclusions:

Patients with early RA who had elevated serum levels of CXCL9 or CXCL10 prior to DMARD therapy had greater difficulty in achieving remission during the first year of treatment. This predictive information was not apparent from standard biomarkers of disease activity. Measurement of these chemokines at disease onset may help in the management of patients with early RA.

To cite this abstract, please use the following information:
Emkey, Gregory R., Strle, Klemen, Antolini, Christopher R., Collier, Deborah S., Seton, Margaret, Khosroshahi, Arezou, et al; Elevated Levels of CXCL9 or CXCL10 in Sera of Patients with Early RA Predict Greater Difficulty in Achieving Remission during the First Year of Treatment. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :25
DOI: 10.1002/art.27795

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