Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis

Inclusion Criteria: * Meet established criteria for diffuse or limited systemic sclerosis (SSc) and evidence of pulmonary at high risk of progression with or without progressive skin disease. * Definition includes subjects who meet the American College of Rheumatology criteria for scleroderma * High Risk of disease progression (see rationale) will be defined as follows * If first non-Raynaud's manifestation of SSc \< 36 months, then if any of the following are true: FVC \<70% predicted or high-resolution computed tomography (HRCT) maximum fibrosis score \>3 or FVC \< 85% and modified Rodnan skin score (mRSS) increase \> 5 over 6 months Regardless of disease duration * Fall in FVC \> 10% over the preceding 12 months or less in the absence of prior therapy or another identified causative process as assessed by the primary scleroderma physician * Fall in FVC \> 10% over 6 months on at least 12 months of prior therapy * Age \> 18 years * Ability to give informed consent. * Willingness to discontinue present therapy for the duration of the study * Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. * Male subject agrees to use an acceptable method for contraception for the duration of the study. * No evidence of acute infection * Absolute neutrophil count \>1000 * Platelets \>75,000 * Stable mycophenolate mofetil dose for 16 weeks Exclusion Criteria: * Inability to give informed consent or comply with protocol procedures * FVC \< 40% or diffusing capacity of carbon monoxide (DLCO) \<30% predicted * Patient has a platelet count of less than 50,000 within 14 days before enrollment. * Patient has an absolute neutrophil count of less 1000 within 14 days before enrollment. * Patient has a calculated or measured creatinine clearance of \< 20 ml/minute within 14 days before enrollment. * Patient has Grade 2 peripheral neuropathy by history within 14 days before enrollment. * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. * Patient has hypersensitivity to bortezomib, boron or mannitol. * Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (- hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. * Patient has received other investigational drugs within 4 weeks before enrollment * Serious medical co-morbidity which in the opinion of the investigator makes participation in the study too high risk * Psychiatric illness likely to interfere with participation in this clinical study.