Research shines light on role of interferon alpha in lupus

[Guest guest]

May 19, 2004

Research shines light on role of interferon alpha in lupus

New York, NY - Interferon alpha may prove to be the chief cytokine involved

in systemic lupus erythematosus (SLE) in a manner similar to the role played

by tumor necrosis factor-alpha (TNF-) in rheumatoid arthritis (RA),

according to new research presented at the 7th International Congress on

Systemic Lupus Erythematosus and Related Conditions [1].

Provocative work presented by Dr Virginia Pascual (University of Texas

Southwestern Medical Center and Baylor Institute for Immunology Research,

Dallas) showed that approximately 95% of pediatric SLE patients have

evidence of exposure to elevated levels of interferon alpha in their blood

cells. To arrive at these findings, Pascual conducted gene microarray

analysis of pediatric patients' blood cells.

This work on interferon alpha in lupus " is extremely important, " commented

conference chair Dr G Lahita (Jersey City Medical Center, NJ). " It's

an amazing clue to the cause of lupus. "

Correlations with SLE disease activity

The new findings build on an initial report published in 2001 in Science

[2], which showed that dendritic cells are activated in patients with lupus

due to exposure to interferon alpha. When stimulated with interferon, the

dendritic cells can induce strong immunity, eventually leading to

autoimmunity, which is the hallmark of SLE, Pascual explains. For this

study, laboratory analyses were run on blood samples taken from 70 lupus

patients (aged 7 to 18 years) and a similar number of age-matched controls.

The analyses found that dendritic cells are produced very efficiently when

blood cells from normal donors were cultured with the serum from lupus

patients. Then the researchers identified interferon alpha as the primary

substance responsible for this effect. Pascual et al concluded that the

capacity of SLE patients' serum to induce dendritic cell differentiation

correlated with disease activity and depended on the actions of interferon

alpha.

Expanding on these initial findings, Pascual tells rheumawire that " the

bottom line is that in children with SLE, more than 90% have been exposed to

high levels of this cytokinethat's more than adult patients. In adults,

about half have evidence of exposure. "

Pediatric patients are a more homogenous group and have more severe disease,

which may explain the difference, she suggests. In addition, pediatric SLE

patients, unlike their adult counterparts, provide an opportunity to obtain

blood samples at the time of diagnosis and before they have taken any

disease-modifying medication.

She added that the majority of pediatric SLE patients are newly diagnosed

and untreated, so it's easier to find cytokine deregulation in these

patients.

Marker of disease activity?

Some of the genes that are up- and downregulated by interferon alpha

correlate with disease activity, Pascual explained in an interview. " In the

future, this may be useful to predict flares and determine who is and who is

not responding to medication, " she says.

While this work is still ongoing, it may one day offer a more reliable

measure than other clinical parameters of disease activity and classical

serology, Pascual says. It may actually be easier than other tests because

just 1 gene is neededrather than the addition of many clinical and

serological data, she says. " It may be a very nice tool to measure disease

flares and response to new medication, " she tells rheumawire.

Role of TNF in SLE highlighted

In her talk, Pascual also commented on " the interesting interplay " between

interferon alpha and TNF- in SLE. " Blocking 1 may promote the production of

the other, " she says.

" TNF promotes the maturation of the dendritic cells that make interferon

alpha, and when these cells mature, they block production of interferon

alpha, " she explains.

Whether or not TNF blockade is a useful therapy in SLE is controversial, but

using TNF blockers as a treatment for SLE may be depend on the disease

stage, Pascual says. Some research has shown that TNF- may promote

inflammation in tissues such as the kidneys in people with SLE. " It may be a

good thing to block TNF in later stages, but not in earlier stages of

disease, " she says.

" It's important to know at what stage we are seeing the patients, " she says.

" This is a developing concept that I think will be very important when

determining how to treat patients. "

Mann

Sources

1. Pascual V. Presentation: Role of interferon alpha in SLE. New York, NY:

7th International Congress on Systemic Lupus Erythematosus and Related

Conditions: Kunkel society session; May 9-13, 2004:NA.

2. Blanco P, Palucka AK, Gill M, Pascual V, Banchereau J. Induction of

dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus.

Science 2001 Nov 16; 294(5546):1540-3.