This is a Phase I, randomized, placebo-controlled, double-blind, dose-escalation study of single and repeat doses of rhuMAb IFNalpha, administered through the SC or IV route, in adults with Systemic Lupus Erythematosus.

Inclusion Criteria:

• For patients with reproductive potential (males and females), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, physical barrier) throughout their participation in the study
• Diagnosis of SLE according to current American College of Rheumatology (ACR) criteria
• Disease duration of ≥ 1 year (after first diagnosis by a physician)
• Current immunity to measles, mumps, rubella, and varicella, as evidenced by positive IgG titers at the time of screening
• Current vaccination against influenza unless contraindicated in the investigator's judgment
• Normal Pap smear within the applicable time interval recommended by current American Cancer Society guidelines

Exclusion Criteria:

• Presence of active lupus nephritis
• Presence of active central nervous system (CNS) disease requiring treatment with high-dose corticosteroids or immunosuppressive agents
• Presence of active vasculitis requiring treatment
• History of arterial or venous thromboses within 12 months of screening
• Moderate to severe anemia, thrombocytopenia, or neutropenia
• Any manifestation likely to require, in the investigator's judgment, treatment with high-dose corticosteroids or the addition of an immunosuppressive regimen during the course of the trial
• Pregnancy or lactation
• Lack of peripheral venous access
• History of alcohol or substance abuse within 6 months of screening
• History of severe allergic or anaphylactic reactions to antibodies or fusion proteins
• Evidence of significant uncontrolled concomitant diseases
• Significant laboratory or electrocardiogram (ECG) abnormalities
• Evidence of any clinically significant abnormality on a chest X-ray
• Severly impaired renal function
• Impaired hepatic function
• Poorly controlled diabetes
• Conditions other than SLE that could require treatment with corticosteroids
• History of malignancy except completely excised basal cell carcinoma
• Congenital immune deficiency
• Positive tests for antibodies to HIV, hepatitis B (HBS antigen, anti-HBC) or C
• Positive IgM antibody titers in the presence of negative IgG titers to Epstein-Barr virus (EBV) or cytomegalovirus (CMV)
• Frequent recurrence of herpes lesions
• Episode of shingles within one year of screening
• Positive screening test for latent mycobacterium tuberculosis infection
• History of severe systemic bacterial, fungal, viral, or parasitic infections within the year prior to screening
• Any current or recent signs or symptoms of infection
• Received antibiotics orally (PO) during the 30 days prior to screening or IV antibiotics during the 60 days prior to screening
• Received a live vaccine within the 30 days prior to screening
• Has been hospitalized within the 30 days prior to screening
• Received > 20 mg/day prednisone for > 3 days during the 30 days prior to screening
• Received azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, pulse dose corticosteroids, intravenous immunoglobulin (IVIG), or transfusions within 6 months prior to screening
• Received cyclophosphamide within 2 years prior to screening
• Received a monoclonal antibody during the 12 months prior to screening
• Previously received an investigational treatment directed against interferon alpha
• Received B-cell depleting therapy (e.g., anti-CD20, anti-CD22)
• Received investigational treatment during the 30 days prior to screening