The purpose of the study is to better understand the factors present in the cells of inflamed joints of patients with arthritis that may cause rheumatoid arthritis. Knowledge gained from this study may lead to new and better therapies for arthritis.

Blood samples will be collected from patients that have been diagnosed with RA based on ACR classification criteria. The study will include 200 donors. The total number of subjects are divided into two groups to yield a power of 95% at a type I error 5% level [determined based on the preliminary data]. In the first group, 200 donors will be treated with methotrexate, plaquenil and/or prednisone (Disease modifying anti rheumatic drugs; DMARDs) that either achieve remission (Disease activity score, DAS28<2.6) or do not achieve remission (DAS28>2.6). 50 donor will be utilized as they respond to DMARDs and achieve remission (DAS28<2.6) and 150 donors that do not respond to DMARDs will be transferred to second group. In the second group, 150 donors will be treated with methotrexate, plaquenil and/or prednisone and Cimzia® (provided to us by UCB).

In the first group of patients, blood samples will be obtained from RA patients treated with Disease modifying anti rheumatic drugs (DMARDs) such as methotrexate, plaquenil and/or prednisone that achieve remission (DAS28<2.6). The patients that achieve remission (DAS28<2.6), blood will only be taken once at the patients routine visit.

The second group will consist of RA patients that did not respond to "DMARDs". These patients will further receive (DMARDs) such as methotrexate, plaquenil and/or prednisone as well as Cimzia® (provided to us by UCB) free of charge. Cimzia® is a FDA approved drug and is a standard of care. Blood samples will be obtained from the patients treated with DMARDs including methotrexate, plaquenil, and/or prednisone and Cimzia® (provided to us by UCB) that have inactive remission (DAS28<2.6). In this group, blood samples will be collected onset of the study as well as 3 and 6 months after treatment with Cimzia at patient's visit through our collaboration with the aforementioned rheumatologists. Patients receiving intra-articular steroid injections will be excluded from the study.

PB mononuclear cells will be isolated from RA whole blood and drawn into Blood collection tubes and isolated by Histopaque gradient centrifugation. Monocytes will be isolated from RA PB mononuclear cells by negative selection (as shown in the preliminary data) and half of the monocytes will be differentiated to macrophages for 7 days. The expression levels for IL-7 and IL-7R will be determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry analysis.

In our statistical analysis, we will first perform a stratified analysis to evaluate the differential expression levels in RA patients with active and inactive disease, controlling for the type of treatment. Data analysis will be performed in collaboration with an UIC Center for Clinical and Translational Science statistician. Specifically, we will perform the comparison of IL-7 and IL-7R expression among RA patients with active (DAS28>2.6) vs. inactive disease (DAS28<2.6) for DMARDs group (group 1). We will then perform a similar comparison for the DMARDs and Cimzia® therapy group (group 2). The stratified analysis can adjust for the potential confounding effect of treatment received and allows for the detection of the potential differential relationships between expression levels of IL-7 or IL-7R and disease status. We will also perform a pooled regression analysis in which the expression logarithm of IL-7 or IL-7R from patients is regressed on the treatment group indicator [DMARDs (group 1) versus on DMARDs plus Cimzia® therapy (group 2)] and disease status (active or inactive disease) which would demonstrate the interaction between treatment groups and disease activity. Such an analysis pools subjects from two treatment groups together and can therefore increase the sample size, and hence potentially the power of detecting the relationships between biomarkers and disease status. The RA samples will be collected over a 2 year period and the data will be analyzed in the last year of the proposal.

Inclusion Criteria:

1. Must meet 1987 Revised Criteria for the Classification of Rheumatoid Arthritis defined as the diagnosis of the referring physician.
2. Persistent knee swelling (>ARA grade 2) for 2 weeks, and no recent intra-articular corticosteroid injection.
3. Age 18 years and older.
4. Must be on Disease modifying anti rheumatic drugs (DMARDs) such as methotrexate, plaquenil and/or prednisone.

Exclusion Criteria:

1. Patients having received intra-articular corticosteroid joint injection within the last 2-4 weeks.
2. Patients with active systemic or joint infections.
3. Women who are pregnant (pregnancy status will be self-reported)
4. Patients under 18 years of age
5. Non-English speakers