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Biochemical Markers of Disease Activity

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

Biochemical Markers of Disease Activity

A major goal in lupus research is to find biomarkers—proteins, enzymes or other molecules—that could provide a "canary-in-the-minefield" early warning system of a lupus flare, enabling doctors to prophylactically treat patients and avoid the flare and the ensuing organ damage. Such biomarkers would also provide important information for clinical trials evaluating the effect of treatment. This is an area in which the ALR has awarded millions of dollars in grants over the past few years.

Among this year's reports:

Interferon and Lupus

Two ALR grantees, Emily Baechler Gillespie, PhD, of the University of Minnesota, and Timothy W. Behrens, MD, currently with Genentech in San Francisco, were among the authors of a paper presented early in the conference validating the role of immune system cells called interferon (IFN)-regulated chemokines as predictors of lupus flare.

Previously, they reported on three chemokines identified in 373 patients who were followed for one year. In this study, they reported that the strongest link occurred with one of those proteins, IP-10, suggesting measuring levels of just that one molecule could help doctors predict upcoming flares.viii

Another presentation by ALR-grantee Mariana J. Kaplan, MD, of the University of Michigan in Ann Arbor demonstrated greater IFN activity in women with carotid plaque and overall lupus disease activity than in women without. They also showed that levels of circulating apoptotic endothelial cells might be another marker for blood vessel damage.ix

What this means for people with lupus? Measuring levels of these biomarkers in blood samples could enable doctors to predict future flares and begin treatment to prevent them, as well as identify women at greatest risk of cardiovascular disease.

Biomarkers for Lupus Nephritis

Canadian researchers presented a study conducted in 22 people with lupus nephritis undergoing a kidney biopsy. The researchers measured concentrations of four proteins in the participants' urine and then compared the protein levels to those in healthy people. When the researchers created a score for the four molecules, they found that patients with active lesions on their kidneys had a much higher increase in the score than patients with kidney scarring or chronic disease.x

What this means for patients with lupus? Tracking these four cytokines could enable doctors to evaluate and monitor kidney health in people with lupus nephritis instead of requiring a more invasive biopsy.

Lupus and Flu Vaccines: The Latest

One of the more timely presentations at the ALR conference focused on the impact of clinical and demographic features related to response to the influenza vaccine.

Because people with lupus have an increased risk of complications from the flu (regular flu or H1N1) due to immune defects and use of immunosuppressants, they should be vaccinated. But some studies find their immune system doesn't respond as well to the vaccine as that of people without lupus. There is also some evidence suggesting that the vaccine can stimulate new or increased autoantibody production, possibly triggering disease activity.

Sherry R. Crowe, PhD, of the Oklahoma Medical Research Foundation presented data showing that African-Americans with milder disease responded best to the vaccine, with Caucasians three times more likely to be poor responders. Poor responders were also more likely to be taking prednisone when they were vaccinated, to have hemolytic anemia and other blood disorders and to have more clinical signs of the disease.

However, the researchers found no difference in baseline autoantibodies between low and high responders, although low responders were more likely to have an autoantibody increase after receiving the vaccine while high responders were more likely to have a decline. Within the six weeks after vaccination, low responders were also more likely to have a flare.xi

What this means for patients with lupus? This study provides important information to help researchers conduct more studies to identify the best approach to giving flu vaccines in people with lupus to ensure the greatest immune response.


References

viii Bauer JW, Petri M, Batliwalla F et al. Validation of Interferon-Regulated Chemokines as Predictors of Lupus Flare; Presented at 73th Annual Scientific Meeting of the American College of Rheumatology, October 17-21, 2009; Philadelphia, PA.

ix Zhao W, Somers EC, McCune WJ, Kaplan MJ. Type I Interferon Gene Signatures Are Associated with Vascular Risk and Atherosclerosis in Systemic Lupus Erythematosus. Presented at 73th Annual Scientific Meeting of the American College of Rheumatology, October 18, 2009; Philadelphia, PA.

x Landolt-Marticorena C, Reich H, Morrison S, et al. Urine Cyto/Chemokines Correlate with Renal Histopathology in Systemic Lupus Erythematosus. Presented at the 73th Annual Scientific Meeting of the American College of Rheumatology, October 17-21, 2009; Philadelphia, PA.

xi Crowe SR, Anderson JR, Dedeke AB, et al. Impact of Clinical and Demographic Features On Influenza Vaccination Responses in Human Systemic Lupus Erythematosus. presented at the 73th Annnual Scientific Meeting of the American College of Rheumatology, October 17-21, 2009; Philadelphia, PA.

 

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

The 2009 American College of Rheumatology Meeting Special Report was made possible in part by generous support from Biogen Idec, Genentech and Johnson & Johnson.

Genentech Biogen IdecJohnson & Johnson

©2009 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.

 


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