The relationship between defects in lymphocyte production of transforming growth factor-beta(1) in systemic lupus erythematosus and disease activity or severity

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.