Chaim Putterman, MD

Albert Einstein College of Medicine, Bronx, NY

2008 Biomarkers
2001 Kidney
2001 Biomarkers

LRI Class of 2008 Consortium Grant with Chandra Mohan, MD, PhD, at the University of Texas, Southwestern, in Dallas.

Lupus nephritis is common in people with lupus, and can cause irreversible kidney damage. The need for biomarkers (“early predictors”) to detect problems and monitor treatment effectiveness is urgent.

With LRI funding, and working from their respective laboratories in the Bronx and Dallas, Drs. Putterman and Mohan will evaluate the power of five urine biomarkers that have shown promise in predicting the onset and progression of lupus nephritis in mice by testing them in urine from people.

The consortia, a powerful pooling of talent and technology that the LRI was willing to consider for ‘human lupus biology’ research, will also study the value of these biomarkers in monitoring and measuring response to therapy. By using human tissue—in this case, urine from people with lupus—the investigators are more likely to make discoveries directly relevant to humans.

If successful, the study could represent a major breakthrough with potentially immense impact on better managing lupus nephritis.

LRI Class of 2001

Dr. Putterman and his team won an LRI grant to unravel the mystery as to why some people with lupus develop kidney disease and others do not.

In work he did previous to the LRI grant, Dr. Putterman found evidence that antibodies that recognize both DNA and kidney-specific antigens could contribute to kidney damage in lupus. The LRI grant was to identify kidney antigens that cross-react with anti-DNA auto-antibodies in lupus.

“Antibodies against DNA are commonly found in the blood of people with lupus. Inflammation of the kidneys, which affects many lupus patients, is believed to result from damage by these antibodies to the specialized kidney cells involved in removing waste materials from the blood. The answers as to why and how the DNA antibodies actually damage the kidney cells have been unclear.

Our work has been focused on identifying the target of the DNA antibodies in the kidney. We are also interested in how subtle differences in the structure or amount of the target in the kidney between individuals may explain why some lupus patients are more susceptible than others to kidney disease. With a grant from the LRI, we have used mouse models that have allowed us to make exciting progress in finding answers to some of these questions. We have also started to extend our initial findings to human lupus.”

Dr. Putterman has found that mice and humans with lupus carry anti-DNA autoantibodies that cross-react with a-actinin, a protein that may be important for kidney function.

“Using a DNA antibody that triggers lupus-like kidney disease in mice, we identified as the target of the antibody a kidney protein called alpha-actinin. Lupus mice had high titers (levels) of antibodies to alpha-actinin in their serum. Furthermore, the kidneys from sick lupus mice were found to have increased amounts of the antibodies that bound alpha-actinin. The finding that alpha-actinin was a possible target for anti-DNA antibodies confirmed previous work by another research team, Eilat and colleagues, who found that anti-DNA antibodies that can damage the kidney also bound to alpha-actinin.

Extending these findings to human lupus, we have found that human DNA antibodies from patients with active disease also bind to alphaactinin, as well as to other, as yet unidentified kidney proteins.

Our current experiments are focused on isolating the additional targets of these damaging antibodies. The results will help us learn more about whether there are inherited differences among people in the genes directing the production of these protein targets, and whether these differences correlate with the risk of kidney damage.”

With the help of two collaborating groups, Dr. Putterman is investigating whether the presence of antibodies to a-actinin is diagnostic of lupus and prognostic of disease severity in people. If subsequent larger clinical studies confirm the usefulness of a-actinin antibodies as a biomarker in lupus diagnosis and prognosis, Putterman plans to register patents for these antibodies as diagnostic tools.

“Our studies, along with those from many other laboratories intensively studying lupus, may be able to answer why individual lupus patients are susceptible to kidney injury. Our LRI-funded research program will hopefully also lead to improved methods of monitoring patients, and open up possibilities for development of new treatments.”

Dr. Putterman has been invited to present his LRI-funded research at national and international conferences.

His research findings also have been published extensively.

Select publications:

Urine Proteome Scans Uncover Total Urinary Protease, Prostaglandin D Synthase, Serum Amyloid P, and Superoxide Dismutase as Potential Markers of Lupus Nephritis. J Immunol. 2010 Published online January 11. Wu T, Fu Y, Brekken D, Yan M, Zhou XJ, Vanarsa K, Deljavan N, Ahn C, Putterman C, Mohan C.

Alpha-actinin is a cross-reactive renal target for pathogenic anti-DNA antibodies. Deocharan B, Qing X, Lichauco J, Putterman C. J Immunol. 2002 Mar 15;168(6):3072-8.

Is alpha-actinin a target for pathogenic anti-DNA antibodies in lupus nephritis? Mason LJ, Ravirajan CT, Rahman A, Putterman C, Isenberg DA. Arthritis Rheum. 2004 Mar;50(3):866-70.

Cross-reactivity of human lupus anti-DNA antibodies with alpha-actinin and nephritogenic potential. Zhao Z, Weinstein E, Tuzova M, Davidson A, Mundel P, Marambio P, Putterman C. Arthritis Rheum. 2005 Feb;52(2):522-30.

Is alpha-actinin a target for pathogenic anti-DNA antibodies in lupus nephritis? Mason LJ, Ravirajan CT, Rahman A, Putterman C, Isenberg DA. Arthritis Rheum. 2004 Mar; 50(3):866-70.

Antigenic triggers and molecular targets for anti-double-stranded DNA antibodies. Deocharan B, Qing X, Beger E, Putterman C. Lupus. 2002;11(12):865-71.

New approaches to the renal pathogenicity of anti-DNA antibodies in systemic lupus erythematosus. Putterman C. Autoimmun Rev. 2004 Feb;3(2):7-11.

Ongoing funding:

In 2003, Dr. Putterman was awarded a $875,000 NIAMS grant to continue this work, and later won a $3.5 million NIH Program Grant.

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