Anti-malarials most effective in lupus patients genetically at risk of high levels of TNF-alpha

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Anti-malarials most effective in lupus patients genetically at risk

of high levels of TNF-alpha

Anti-malarial drugs are most effective in people with lupus who are

genetically predisposed to high levels of tumour necrosis factor

alpha and low levels of the cytokine IL-10. A study published today

in the journal Arthritis Research & Therapy reveals that anti-

malarial drugs, widely used to treat systemic lupus erythematosus

(SLE), bring serum levels of tumour necrosis factor alpha (TNF-alpha)

back to normal in SLE patients. The research shows that these drugs

are more effective in patients who have two specific genetic

variations (polymorphisms) on the TNF-alpha and IL-10 genes that

predispose them to abnormally high levels of TNF-alpha and low levels

of the cytokine IL-10. This finding may have important clinical

applications through the identification of lupus patients who are the

most likely to benefit from anti-malarial therapy.

, from the University of Oviedo in Spain and colleagues

from the Hospital Universitario Central de Asturias in Oviedo matched

192 SLE patients with 343 healthy individuals to act as controls. The

researchers genotyped both patients and controls for two specific

polymorphisms on the TNF-alpha and IL-10 genes. et al. then

measured TNF-alpha serum levels in 171 of the SLE patients and 215 of

the controls. The patients were asked precise questions regarding any

treatment received before the study.

et al.’s results show that, as expected, average TNF-alpha

serum levels were higher in the population of SLE patients (33.57pg/

ml) than in the group of controls (19.66 pg/ml). However, patients

who had been taking anti-malarial drugs for at least three months

before the study had serum levels of TNF-alpha (16.64 pg/ml) similar

to those of controls. Patients who had not been taking the drugs

before the study had much higher levels of TNF-alpha (60.78 pg/ml).

et al. found that, in patients with both polymorphisms, TNF-

alpha levels were four times lower if the patient had been taking

anti-malarial drugs. For patients who do not have the polymorphisms,

the difference in TNF-alpha levels was much less significant between

patients who were on anti-malarial therapy and patients who were not.

Patients with both polymorphisms had a four times higher probability

to respond well to anti-malarial therapy (and not need any other

therapy) than other patients.



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