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ACR Special Report: Philadelphia, PA, October 18-21, 2009

ALR-Supported Research Focus of Plenary Session

Christine McBurney, MD, of the University of Pittsburgh, presented the results of work supported, in part, by the ALR during one of the plenary sessions at the ACR. She focused on the linkages between C4d, a remnant product from complement, a component of the immune system, which is deposited on red blood cells.

Earlier studies found abnormal levels of C4d on the red blood cells of people with lupus. They also found that C4d levels were significantly associated with disease activity and central nervous system involvement, including seizures and psychosis; and, in a non-lupus population, with stroke. In this study, McBurney and her colleagues, including ALR grantee Joseph Ahearn, MD, also of the University of Pittsburgh, evaluated C4d levels in 356 patients with lupus over 8 years. They found that higher levels of C4d were associated with higher levels of disease activity and blood clotting abnormalities. Patients with higher levels were twice as likely to have experienced cardiovascular events, particularly stroke and pulmonary embolism. They also had a fivefold increased risk of a stroke. C4d levels were also independently associated with death from any cause, with patients with high C4d levels having a nearly eightfold risk of death compared to those with lower levels.

C4d, said McBurney, “May provide a link between complement activation systemic inflammation and thrombosis, including stroke.”xiii

Key point: This study suggests that C4d may provide a biomarker to assess patient risk of stroke, cardiovascular disease, and death.

ALR grantee Susan A. Boackle, MD of the University of Colorado-Denver School of Medicine delivered the REF Edmond L. Dubois, MD, Memorial Lectureship. Her topic, “The Path from Gene to Function: Analysis of a Lupus Susceptibility Gene c/r,” examined her own journey to pin down the role of the gene, complement receptor 2 (CR2), in the pathogenesis of lupus.

Johnson & Johnson       Genetech/Biogen

More information about lupus and treatment advances can be found by visiting www.lupusresearch.org.

The 2010 American College of Rheumatology Meeting Special Report was made possible in part by generous support from Biogen Idec, Genentech and Johnson & Johnson.

©2010 Alliance for Lupus Research. All Rights Reserved.

Contents herein may not be reproduced, republished or distributed without the prior written permission of the Alliance for Lupus Research. To request permission to reproduce, republish or distribute any part of this report, contact us at 212-218-2840 or email info@lupusresearch.org.


i Bingham CO, et al. Citrullination and Peptidylarginine Deiminase (PAD) Expression Is Detected in the Oral Mucosa and Periodontium in the Absence of Rheumatoid Arthritis.
ii Scher JU, et al. Characteristic Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA): A Trigger for Autoimmunity?
iii Merrill JT, et al. Five-Year Experience with Belimumab, a BLyS-Specific Inhibitor, in Patients with Systemic Lupus Erythematosus (SLE).
iv Vollenhoven RF, et al. Belimumab, a BLyS-Specific Inhibitor, Reduced Corticosteroid Use in Patients with Active SLE: Results from the Phase 3 BLISS-52 and -76 Studies.
v Petri MA, et al. Belimumab, a BLyS-Specific Inhibitor, Reduced Disease Activity, Flares, and Prednisone Use in Patients with Seropositive SLE: Combined Efficacy Results from the Phase 3 BLISS-52 and -76 Studies.
vi Chatham WW. Effect of Belimumab, a B-Lymphocyte Stimulator–Specific Inhibitor, on Functional Antibodies to Pneumococcal, Tetanus, and Influenza Vaccines.
vii Stohl W. Belimumab, a BLyS-Specific Inhibitor, Significantly Reduced Autoantibodies, Normalized Low Complement, and Reduced Selected B-Cell Populations in Patients with Seropositive Systemic Lupus Erythematosus (SLE): The Phase 3 BLISS Studies.
viii Wallace DJ, et al. Epratuzumab Demonstrates Clinically Meaningful Improvements in Patients with Moderate to Severe Systemic Lupus Erythematosus (SLE): Results from EMBLEM™, a Phase IIb Study.
ix Kalunian KC, et al. BILAG-Measured Improvement in Moderately and Severely Affected Body Systems in Patients with Systemic Lupus Erythematosus (SLE) by Epratuzumab: Results from EMBLEM™, a Phase IIb Study.
x Sullivan BA, et al. A Flow Cytometric Receptor Occupancy Assay Demonstrates Dose-Dependent Blockade of B7RP-1 by AMG 557 on Circulating B Cells from SLE Subjects.
xi Fleischmann RM. Evidence of Peripheral B Cell Depletion in Subjects with Controlled Systemic Lupus Erythematosus (SLE) Following Subcutaneous Administration of SBI-087.
xii Salwsky KA, et al. A Systematic Literature Review of the Direct Costs of Systemic Lupus Erythematosus (SLE) in the United States (US).
xiii McBurney CA. Platelet C4d Is Associated with All-Cause Mortality in Patients with Systemic Lupus Erythematosus.
xiv Bernatsky SR, et al. Further Defining Cancer Risk in Systemic Lupus: Updated Results in an Expanded International Multi-Centre Cohort
xv Hanly JG, Urowitz MB, Sanchez-Guerrero J, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum. 2007;56(1):265-73.
xvi Izmirly PM, et al. Hydroxychloroquine and Prevention of Anti-SSA/Ro Associated Cardiac Disease in Mothers with a Previous Child with Neonatal Lupus

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