Centocor Microarray Study of Patients

Specific Aim 1. To determine the transcriptome of peripheral blood mononuclear cells isolated monocytes and target tissues in IMIDs.

Specific Aim 2. To analyze the change in gene expression profiles in patients with Crohn's disease, psoriatic and rheumatoid arthritis before and after infliximab therapy.

Our hypothesis is that hematopoietic stem cells are very sensitive to elevated levels of TNFa, which potentiates their differentiation into myeloid effector cells. During their migration from the bone marrow to the end organ, these cells express a unique set of genes that function to prime these cells to respond to critical differentiation signals. Elucidation of this transcriptome through microarray analysis will provide insight into novel drug targets and a formal understanding of the biochemical and molecular genetic events linking IMIDs. To test our hypothesis, will determine the transcriptome in peripheral blood mononuclear cells and isolated monocytes from 20 normal healthy donors, 10 patients with psoriatic arthritis, 10 patients with psoriasis, 10 patients with Crohn's disease and 10 patients with rheumatoid arthritis. The transcriptome will also be examined in inflamed intestinal tissue from patients with Crohn's disease, psoriatic skin and synovial tissue from patients with rheumatoid and psoriatic arthritis.

Eligibility Criteria:
Inclusion Criteria:

Rheumatoid Arthritis

* 18 years of age or older
* 3 years duration of disease or less
* Must meet ACR criteria
* 3 tender or swollen joints
* Positive RF or anti-CCP antibodies or evidence of erosions on plain radiographs
* CRP \> 1.5
* Non-responder to methotrexate, but on a stable dose of 12.5 to 20 mg/week
* Only subjects scheduled to receive infliximab as part of their care are eligible to participate.

Crohn's disease

* 12 years of age or older
* Clinical and endoscopic confirmation of disease
* CDAI \> 220 or evidence of intestinal inflammation on endoscopy
* Documented failure to conventional therapy.
* Only subjects scheduled to receive infliximab as part of their care are eligible to participate.

Psoriatic arthritis

* 18 years of age or older
* Must meet CASPAR® criteria for diagnosis
* RF and anti-CCP negative
* 3 tender or swollen joints
* Non-responder to methotrexate, but on a stable dose of 12.5 to 20 mg/week
* Only subjects scheduled to receive infliximab as part of their care are eligible to participate.

Psoriasis

* 18 years of age or older
* Total BSA \> 5%

Exclusion Criteria:

* Candidates for whom the procedures would be medically contraindicated would be excluded.
* Patients with any active infections (viral or bacterial) will not be considered for inclusion into the trial.
* Patients with history of chronic infection such as hepatitis, pneumonia or chronic pyelonephritis; those with current signs or symptoms of severe or progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease including demyelinating disease such as multiple sclerosis.
* Those with history of lymphoproliferative disease such as lymphoma or signs suggestive of lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, supraclavicular, epitrochlear, or periaortic areas), or splenomegaly will be excluded.
* Patients with concomitant diagnosis of CHF, including medically controlled asymptomatic patients will not be eligible to participate.
* Any current known malignancy or history of malignancy in the last 10 years will be excluded. History of basal cell carcinoma is not excluded.
* Those with known bacterial, tuberculosis or opportunistic infections including but not limited to evidence of active cytomegalovirus , active Pneumocystis carinii, aspergillosis, or atypical mycobacterium infection within the previous 6 months will be ineligible.
* Those with known infection with Human immunodeficiency virus (HIV) or known active hepatitis B or C (including associated active hepatitis) will be excluded.
* Known substance abuse (drug or alcohol) within the previous 3 years.
* Patients who have previously taken anti-TNF therapy are not eligible.
* Patients who have been treated with DMARDS, biologic or investigational agents must wash out for at least 6 weeks prior to enrollment with the exception of those on methotrexate, who must be on a stable dose at least 2 weeks prior to start of study.
* Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.
* Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.
* Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB.
* Have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to screening.