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Wayne State Team Developing Array for Pulmonary Sarcoidosis Diagnosis, Drug Target Discovery


By Molika Ashford

Researchers at Wayne State University are developing an antigen microarray that they hope will aid in the diagnosis of sarcoidosis as well as support research into the disease’s immunologic origins and organ specificity.

The group received a one-year $180,000 grant in December from the National Heart Lung and Blood Institute in support of the project. The researchers plan to screen the sera of patients with sarcoidosis against RNA extracted from the lymph nodes of sarcoid patients' granulomas to develop a panel of antibodies with high sensitivity and specificity to identify the pulmonary form of the disease.

The project's principal investigator, Lobelia Samavati, told BioArray News that she is confident she will be able to identify a panel of predictive antibodies and create a diagnostic antigen microarray within the time frame of the grant. She said her team hopes it will then be able to win additional funding to support work to refine the array to include a range of organ-specific antigens, which would be important for identifying potential treatment targets in the disease.

Samavati said that though sarcoidosis has been studied for more than a century, the immunologic etiology of the disease is still very opaque.

"The main observation that led us to develop this grant and this project was that [most sarcoidosis patients] have this aberrant immunity," she said.

"So we think that these granulomas form because of a specific pathway, reacting to some type of antigen, but this may be a self-antigen, or may be from outside — viral, bacteria, anything like that," she said.

Samavati said developing targeted treatments for the disease will require teasing out which types of antibodies play a role and what these roles are. The group hopes its array will support such research, as well as eventually provide a diagnostic tool.

"Characterization of informative phages may reveal the presence of… bacterial or viral antigens related to the development of pulmonary sarcoidosis," Samavati wrote in her project abstract. "A long-term objective of this proposal is the identification of organ-specific sarcoidosis antigens that could be useful to diagnose extra-pulmonary forms of sarcoidosis and that could be targeted by drugs or be the basis for immunotherapy."

The group has proposed to start with pulmonary sarcoidosis because the lungs are the most frequently affected by granulomas, the clumps of tissue that characterize the disease.

The researchers plan to screen sera of lung sarcoidosis patients against proteins extracted from the lymph nodes of a cohort of patients with pathologically confirmed disease. This will allow them to identify the serum samples that produce the "highest bands."

Using these samples, they will then screen the sera against T7 phage cDNA libraries created from RNA extracted from the granulomas comparing with two control groups with samples from patients with tuberculosis and rheumatoid arthritis.

"The trick is that everybody has some type of antigens," Samavati said. "The question is which are more specific and sensitive to diagnose this disease."

She said the group has already collected the sera from about 150 patients. It plans to collect 100 tuberculosis samples for the control group, as well as a similar number from RA patients.

She said the fact that the group had already collected almost two-thirds of the necessary samples was an advantage to them in winning the funding for the project.

On the diagnostic front, Samavati said certain kinds of sarcoidosis are easier than others to diagnose using the current methods of tissue biopsy, with lung sarcoidosis actually on the easier side. But if the group is able to continue its work to create an array of additional organ-specific antigens, it could be very useful for clinical diagnosis of some of the more difficult organ types like brain and eye, where tissue biopsies are more difficult and dangerous.

"It’s very important to develop this kind of classification test," she said, adding that she hopes to see it become available in "five to 10 years."

Additionally, once the group has created its initial array, Samavati said she hopes her team and others will be able to use such screening to delve further into the function of the antibodies seen in the disease.

The researchers aren't sure how the array will take shape yet and expect this to become clearer as they move through their project. Samavati said she expects the final sarcoid-specific panel to be about 10 antibodies, based on the group's preliminary research.

"This will have to be further tested in different disease pathologies," she said.

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