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Gene Chips Help Diagnose Leprosy
  
By Nancy Touchette

The pathogen that causes leprosy still cannot be grown in the laboratory; rather, it is grown in the nine-banded armadillo.

Many think of leprosy as a disease from long ago, but the Biblical scourge is still with us today, affecting about six million people worldwide. Each year there are more than 600,000 new cases.

The bacterium that causes leprosy, Mycobacterium leprae, can cause two types of disease that can be difficult to tell apart. Now a new study shows that DNA microarray technology can discriminate between the different subtypes of leprosy.

The severe and infectious form of leprosy described in the Bible is known as L-lep (for lepromatous). Patients often have disfiguring lesions that contain high numbers of bacteria. The much less severe and non-infectious form, which often clears on its own, is known as T-lep (tuberculoid).

“The two forms of the disease are hard to distinguish and the treatments are very different,” says Patrick Brennan, a leprosy expert at Colorado State University in Fort Collins. “This study is exciting because it’s very important to be able to distinguish which is which.”

This image shows acid-fast bacilli characteristic of lepromatous lesions.

The research puts leprosy on a growing list of diseases that can be better diagnosed and classified through genomic profiling than through standard methods such as examining tissues under the microscope.

In addition, the research shows that using DNA microarrays, or gene chips, to examine patterns of gene activity is valuable for another reason. The gene chips revealed that different immune-system genes are activated in different forms of the disease.

Thus, the human body may respond differently when infected by the pathogen. This finding may ultimately help researchers develop new drug targets and better strategies for treating the disease.

In the new study, reported in Science, Robert Modlin and his colleagues at the University of California, Los Angeles, examined the patterns of gene expression from six leprosy patients who had been diagnosed with the less severe form and five with the more severe form.

All five patients with the severe form had the same pattern of gene activity. Five of the patients with the less severe form had a distinct gene profile that differed from the other group. But one of them had a gene signature virtually identical to the other signature.

“When we went back to the original biopsy, we saw that this patient had been misclassified,” says Modlin. “It is not always clear-cut to classify these lesions using the microscope. Genetic profiling may offer an advantage over standard methods.”

Modllin’s team noticed that among the genes more active in patients with the less severe form were genes that activate killer T cells, which attack and destroy invading pathogens.

A different set of immune genes was active in patients with the more severe form. These genes trigger B cells, another type of immune cell that produces antibody proteins.

Modlin does not know why some individuals mount different immune responses to the same microbe. However, he did notice that a gene for an immune protein called LIR-7 was particularly active in patients with the severe form of leprosy. This gene was more than five times more active in these patients compared to the others.

Modlin believes that LIR-7 somehow blocks the pathway that causes killer T cells to attack the invading pathogen. Developing new drugs that target this protein could yield effective treatments for the more severe form of leprosy.

—Related Articles—

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J.R. Bleharski et al. Use of genetic profiling in leprosy to discriminate clinical forms of the disease. Science 301, 1527-1530 (September 12, 2003).
 

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