A. Schattner et al., INDUCED TNF PRODUCTION IN-VITRO AS A TEST FOR FAMILIAL MEDITERRANEAN FEVER, Quarterly Journal of Medicine, 89(3), 1996, pp. 205-210
We have previously demonstrated an altered pattern of tumor necrosis f
actor (TNF) secretion in patients with familiar Mediterranean fever (F
MF). To examine whether TNF determination could assist in diagnosing F
MF, we stimulated heparinized blood of 51 asymptomatic FMF patients wi
th lipopolysaccharide (LPS) and then measured TNF production in respon
se to inducers, compared to unstimulated blood cells and to cells from
a control group of 12 matched healthy subjects. Following LPS pretrea
tment, which induced TNF release, FMF patients produced significantly
less TNF than controls, whether production was 'spontaneous' or induce
d by either LPS or phytohaemagglutinin (p less than or equal to 0.003)
. Such 'exhaustion' did not occur in untreated cells. We then used the
se results to classify a further group of 29 FMF patients and 10 match
ed healthy controls ('validation' group) who underwent the same studie
s. The test correctly identified 25/29 patients as having FMF and 7/10
controls as not having FMF; a sensitivity of 86% and a specificity of
70% (likelihood ratios 2.9 (positive test) and 0.2 (negative)). Ident
ification of a blunted TNF response following previous stimulation by
a simple assay, may help the diagnosis of FMF in asymptomatic patients
, provided it is interpreted in conjunction with supportive clinical d
ata.