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Wednesday, March 26, 2008

What is the topic?

Pneumonia is the most common form of lung disease in lupus patients. The first defense against pneumonia is a person’s immune system, which is called to action and directed by a number of genes.

What did the researchers hope to learn?

The researchers for this study wanted to see if they could identify specific risk factors for pneumonia among lupus patients. Were older patients at greater risk? African Americans more than Caucasians? Did it matter how long a person had lupus, or what medications they had taken? Along with these variables, the researchers were particularly interested in examining how very small differences in the structure of several genes involved in the body’s immune system might increase a lupus patient’s chances of getting pneumonia.

Who was studied?

The researchers analyzed clinical and genetic information on 282 patients (251 women, 31 men) who were part of the Lupus Genetics Project of the University of California, San Francisco. Nearly half (45 percent) were Caucasian, and other ethnic groups represented were Hispanic (18.4 percent), African American (11.7 percent), Asian/Pacific Islander (19.5 percent), and Other/mixed ethnicity (5.3 percent). Of the 282 patients studied, 42 were identified as having had pneumonia sometime after they were diagnosed with lupus.

How was the study conducted?

The researchers compared the patients in the study who had pneumonia with those who did not; the factors they compared were sex, ethnicity, socioeconomic status, age at lupus diagnosis, duration of disease, lupus medications, renal disease, and low white blood cell count (leucopenia). They also looked at small inherited differences in three genes that have previously been associated with high rates of infection. The researchers used complex statistical techniques to weigh the impact of the different factors on the rate of pneumonia.

What did the researchers find?

Being male, having had lupus nephritis or leucopenia, and treatment with immunosuppressive drugs were all associated with a higher risk for getting pneumonia, but the strongest association was a specific variation in a gene that plays a role in the production of a molecule called tumor necrosis factor (TNF). TNF helps cells recognize and defend themselves against foreign bacteria, including the bacteria that cause pneumonia, so any change in the genes that promote TNF may affect the body’s ability to fight off the infection. The researchers did not find evidence linking variations in the other two genes they studied with higher risk for pneumonia.

What were the limitations of the study?

This study relied on data that had already been provided to the Lupus Genetics Project, so the researchers were limited in the categories of information they could examine. They weren’t able to consider such potentially important factors as patient’s immunization histories, the doses of their steroid or immunosuppressant medicines, which increase the risk for infections. Also, they may not have identified all of the patients who had pneumonia owing to incomplete records. The relatively small size of the study population also meant that they may not have had as much genetic variation as they might have needed for important distinctions to show up.

What do the results mean for you?

This research does identify some important risk factors that need to be studied more thoroughly. If, as their findings suggest, specific variations in the TNF gene they studied -- or perhaps another gene yet to be identified -- can be shown to raise a lupus patient’s chances of getting pneumonia, doctors could use this information and recommend a number of measures -- such as pneumonia vaccines or antibiotics -- to help prevent some of these infections in those patients at risk.

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