Researchers at the Wayne State University School of Medicine have developed a novel screening tool that can differentiate between sarcoidosis and tuberculosis antigens and that could lead to earlier reliable diagnosis and treatment of both diseases. It may also aid in the development or evaluation of a tuberculosis vaccine.
The non-invasive technique is now pending patent and answers the need to develop accurate tests to diagnose sarcoidosis and TB reliably and quickly.
“We show for the first time that immuno-screening of a library derived from sarcoidosis tissue, which we developed at Wayne State in Detroit, can differentiate between sarcoidosis and tuberculosis antigens. These results are extremely exciting and we believe these findings can revolutionize the fields of both TB and sarcoidosis,” said study principal investigator Lobelia Samavati, M.D., associate professor of medicine and of molecular medicine and genetics, and director of the Division of Pulmonary, Critical Care and Sleep Medicine’s Center for Sarcoidosis and Interstitial Lung Diseases. “We would like to thank the patients and the community for support and encouragement throughout the process of this study.”
The scientists spent two years developing the sarcoidosis library and two years completing the study. Study participants were from the Detroit area. A practicing physician, Dr. Samavati sees patients with lung diseases, especially sarcoidosis, at Wayne State University Physician Group Internal Medicine clinics in Detroit.
“Sarcoidosis is an inflammatory granulomatous disease of unknown etiology affecting multiple organs, and is highly prevalent in Michigan and especially in Detroit. It affects younger adults, especially African-Americans, and can lead to severe morbidity and mortality,” Dr. Samavati said.
The condition strikes between 20 and 50 of every 100,000 Americans annually, most of them between the ages of 20 and 40. Sarcoidosis attacks African-Americans at least 10 times more often than Caucasians, and women more often than men.
Common symptoms include chest pain, a dry cough and shortness of breath. Researchers have not yet identified a cause or a cure for sarcoidosis, an inflammatory disorder of unknown origin. The condition, which manifests as abnormal clumps of immune cells called granulomas, can affect a number of organs such as lungs, brain, eyes and the skin. In some cases, the condition can go into remission without treatment. Extreme cases can require a heart or lung transplant.
Sarcoidosis is most frequently treated with steroids or other immune suppressive medications. According to the National Heart, Lung and Blood Institute of the National Institutes of Health, many patients recover with few or no long-term problems. More than half experience remission within three years of being diagnosed, but the disease can reappear or lead to slow and progressive lung damage requiring lung transplantation. Organ damage occurs in about one-third of patients. While rarely fatal, death from sarcoidosis is generally caused by advanced lung disease, heart failure or brain damage.
Physicians can only use invasive procedures such as tissue biopsy to diagnose sarcoidosis.
Tuberculosis remains a major global health problem. The World Health Organization estimates that more than one-third of the global population is infected with and/or carries M. tuberculosis, or Mtb, a typically dormant infection. Those infected are asymptomatic and non-contagious.
Five percent to 10 percent of latent Mtb carriers will develop active TB, Dr. Samavati said.
“Therefore, it is important to appropriately diagnose and treat both latent TB infection and active TB disease, as well as to discriminate between non-infectious granulomatous such as sarcoidosis and TB. It is not only locally important but also it is important to control the level of contagion in the environment, and ultimately the health of the global population,” she said. “Current available tests have low yield, especially in developing countries. The current mode of detection and diagnosis of Mtb is generally confirmed through a combination of three different diagnostic tools, such as tuberculin skin test, blood-based interferon-gamma or release assays, or IGRA. Most importantly, to diagnose active disease patients need to have a positive sputum culture to confirm Mtb infection. However, generally this gold standard diagnostic test takes about six weeks to get culture results back. This may lead to late diagnosis, late treatment and spreading of the bacteria.”
Dr. Samavati and team outline their method in “Development of a T7 Phage Display Library to Detect Sarcoidosis and Tuberculosis by a Panel of Novel Antigens,” an open-access article published in March in EBioMedicine, a new journal affiliated with The Lancet and Cell.
The scientists have now contacted the WHO to obtain a large collection of sera from patients with tuberculosis and those with latent TB from various countries.
“Future goals involve the validation of these markers on a larger number of sarcoidosis subjects. Additionally, we will apply our novel technology to test whether we can reliably discriminate between the latent TB and active TB subjects sera that we obtained recently from the WHO,” she said.
Dr. Samavati’s research lab is located in the School of Medicine’s interdisciplinary Center for Molecular Medicine and Genetics, built around modern molecular genetics, and comprising basic researchers, physician-scientists, computational scientists and genetic counselors to increase the understanding, diagnosis, treatment and prevention of human disease. Her research team included Department of Medicine Research Associates Harvinder Talwar, Ph.D., who contributed to the study design and sample processing, and Rita Rosati, Ph.D., who developed the T7 phage library and participated in the initial study design, Henry Ford Health System Department of Public Health Sciences’ biostatistician Jia Li, Ph.D., who contributed to data preprocessing and statistical analysis; Samiran Ghosh, Ph.D., assistant professor of Biostatistics, Family Medicine and Public Health Sciences; who contributed to data processing and statistical analysis; and Félix Fernández–Madrid, M.D., Ph.D., professor of Internal Medicine, who contributed to study design and data analysis.
The work is supported by a grant from the National Heart, Lung, and Blood Institute (R21 HL104481). The provisional patent includes the methods and technique to diagnose sarcoidosis in a subject and the markers that can distinguish a sarcoidosis subject from a healthy subject and/or a subject having tuberculosis.