A distinct subset of HLA-DR+-regulatory T cells is involved in the induction of preterm labor during pregnancy and in the induction of organ rejection after transplantation.

Regulatory T cells (Tregs) are known to suppress alloimmune responses during pregnancy and post organ transplantation. We demonstrate that a distinct subset of FoxP3(+)DR(+)-Tregs among the total CD4(+)CD127(low+/-)CD25(+)-Treg cell pool is critically involved in preterm labor induction and kidney transplant rejection as well. Compared to healthy pregnancies and non-rejecting kidney recipients, we found that the percentage of the FoxP3(+)DR(+)-Treg subset was not reduced, but that the level of HLA-DR expression of such Tregs was strongly diminished in preterm laboring women and in patients with acute renal allograft rejection. In addition, both patient collectives showed a significantly reduced suppressive activity of their circulating CD4(+)CD127(low+/-)CD25(+)-Treg cell pool. Our findings propose that the FoxP3(+)DR(+)-Treg subset may be decisively responsible for the suppressive activity of the total CD4(+)CD127(low+/-)CD25(+)-Treg cell pool and that the immunologic mechanisms leading to preterm labor necessitating preterm delivery may be similar to those leading to allograft rejection after transplantation.

Distinct subsets of regulatory T cells during pregnancy: is the imbalance of these subsets involved in the pathogenesis of preeclampsia?

Regulatory T cells (CD4(+)CD25(+)FoxP3(+)-Treg cells) are important regulators of tolerance induction during pregnancy. We now found that the number of CD4(+)CD25(+)FoxP3(+)-Treg cells decreases during normal course of pregnancy and even more so in women affected by preeclampsia. The functional activity of these CD4(+)CD25(+)-Treg cells was significantly reduced in comparison to those of healthy pregnants. Further analysis revealed two Treg subsets that differed with regard to the FoxP3 and CD25 expression. The percentage of both, CD4(+)CD25(+)FoxP3(high+)-Treg and CD4(+)CD25(high+)FoxP3(+), was maximal in the first and second trimenon, but declined severely in the third trimenon. In preeclamptic women the population of CD4(+)CD25(high+)FoxP3(+)-Treg cells was particularly apparent, while the population of CD4(+)CD25(+)FoxP3(high+)-Treg cells was significantly decreased. We propose that CD4(+)CD25(+)FoxP3(high+)- and CD4(+)CD25(high+)FoxP3(+)-Treg cell populations represent distinct Treg cell subsets, and that disturbances in the balance of these two Treg cell subsets are associated with the presence of preeclampsia, but not HELLP-syndrome.

Procalcitonin as marker of infection in patients with Goodpasture's syndrome is misleading.

BACKGROUND: Procalcitonin (PCT) is routinely measured to differentiate autoimmune disorders from infection. There are reports, however, where PCT is high in the absence of infection, i.e. in vasculitis. To investigate the value of PCT in Goodpasture's syndrome, we reviewed the charts of patients with Goodpasture's syndrome who were treated from 1996 to 2006. METHODS: PCT (normal range<0.5 ng/ml) was measured with an immunoluminometric assay, C-reactive protein (CRP; normal range<5 mg/l) with nephelometry. Anti-glomerular basement membrane antibodies (normal range<1:10) were measured with ELISA. RESULTS: During the last 10 years we diagnosed seven patients with Goodpasture's syndrome. Six out of seven patients had biopsy proven crescentic and necrotizing glomerulonephritis. Five patients had a severe manifestation with pulmonary involvement (n=3) and/or severe renal insufficiency (n=4). Mean CRP levels were 145.7 mg/l, mean PCT levels were 34.1 ng/ml. Therapy consisted of plasmapheresis (n=3), pulse cyclophosphamide therapy (n=4) and glucocorticoids (n=6). Remarkably, all patients with elevated PCT levels had life-threatening disease (n=4) and remained dialysis-dependent (as compared to with only one out of three patients with normal PCT). In two out of five patients with severe Goodpasture's syndrome, PCT levels remained high. After thorough exclusion of infection, resumption of high dose glucocorticoids normalized PCT and CRP levels. CONCLUSIONS: The measurement of PCT as a marker of infection in patients with Goodpasture's syndrome is misleading. High PCT values might rather point to a severe form of Goodpasture's syndrome with a more unfavourable prognosis. However, further studies with larger patient numbers are needed to prove this hypothesis.