The relationship between defects in lymphocyte production of transforming growth factor-beta(1) in systemic lupus erythematosus and disease activity or severity
K. Ohtsuka et al., The relationship between defects in lymphocyte production of transforming growth factor-beta(1) in systemic lupus erythematosus and disease activity or severity, LUPUS, 8(2), 1999, pp. 90-94
Transforming growth factor beta (TGF-beta) comprises of a family of protein
s with pleiotropic signaling properties and potent immunoregulatory effects
. In SLE we recently reported that lymphocyte production of the total and a
ctive forms of TGF beta(1) was decreased. Here we asked whether these defec
ts correlate with disease activity and/or severity. TGF-beta(1) production
by blood lymphocytes from 17 prospectively studied SLE patients was compare
d with 10 rheumatoid arthritis (RA) patients and 23 matched healthy control
s. The RA levels of active TGF-beta(1) were lower than controls, but were n
ot deceased to the extent found in SLE. Levels of constitutive and anti-CD2
stimulated active TGF-beta(1) detected in picomolar amounts were markedly
reduced in six untreated patients hospitalized with recent onset, very acti
ve and severe SLE and similarly reduced in 11 patients with treated, less a
ctive disease. By contrast, decreased production of total TGF-beta(1) inver
sely correlated with disease activity. These studies suggest, therefore, th
at although impaired lymphocyte secretion of the latent precursor of TGF-be
ta(1) may result as a consequence of disease activity, a decreased capacity
to convert the precursor molecule to its active form may pre-date disease
onset. Insufficient exposure of T cells to picomolar concentrations of TGF-
beta(1) at the time they are activated can result in impaired down-regulati
on of 1g synthesis. Therefore, decreased lymphocyte production of active TG
F-beta(1) in SLE could be an immunologic defect which contributes to the B
cell hyperactivity characteristic of this disease.