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

Highlights of the American College of Rheumatology 2010 Annual Scientific Meeting
The Latest Treatment Advances for Lupus
Treatment May Prevent Neonatal Lupus
The Brain and Lupus: 2010 Update
Risk of Some Cancers Double in Lupus
Assessing the Cost of Lupus
From the Lab to the Clinic: Lessons Learned About Lupus
ALR-Supported Research Focus of Plenary Session

Highlights of the American College of Rheumatology
2010 Scientific Meeting

It might sound a bit odd, but what ALR Scientific Advisory Board Chair Mary (Peggy) K. Crow, MD found most interesting from this year’s meeting had to do with rheumatoid arthritis (RA). Specifically, the possibility that bacterial infections in the mouth and stomach could trigger the disease. So why highlight it here when our focus is lupus? “Because it may also apply to lupus in the end,” she said, given that systemic lupus erythematous (SLE) and rheumatoid arthritis share several genetic markers.

Two studies at the ACR meeting focused on bacteria called Porphyromonas gingivalis (P. gingivalis), which causes gum disease. Previous studies have found that people with RA are far more likely to have evidence of P. gingivalis infection than those without the disease. Now researchers have found that the bacteria trigger a process called citrulination, which changes the structure of certain proteins, resulting in the anti-citrullinated protein (ACP) antibodies that are a hallmark of RA.i Another study used DNA sequencing to prove that RA patients have higher levels of Prevoltellacaeae bacteria in their gut than healthy patients, bacteria thought to induce the differentiation of inflammatory Th17 cells in the intestine.ii

“The overall theme is that there is value in considering how environmental microbes such as bacteria and viruses can promote autoimmune disease,” Dr. Crow said, “turning on and off the immune system in ways they shouldn’t.”

Of more interest to the lupus community, she said, is the growing science regarding the role of nucleic acids like DNA and RNA in driving immune responses through proteins called toll-like receptors (TLR). These molecules recognize autoantigens that contain DNA and RNA and can trigger inflammatory responses from interferon alpha, resulting in more damage. In addition, she noted, TLR activation is an important mechanism in promoting B cell activation. The ALR has funded several investigators who are focusing on ways to inhibit TLRs from triggering interferon alpha production.

“None of this was even thought of 10 or 12 years ago,” she said. “I feel like we’ve honed in on a lot of the key mechanisms associated with lupus, particularly the role of TLRs and nucleic acids. For years, everyone knew that anti-DNA antibodies target the proteins associated with lupus, but a big advance in the last 10 years has been our ability to understand that they don’t just target autoantibodies; they play a role in the autoimmune response. The whole concept suggests all sorts of potential drug targets that can come from controlling the ability of nucleic acids to associate with TLRs.”

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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