Recognition of Schistosoma mansoni cathepsins B and L by human IgG1 and IgG4 antibodies.

Human schistosome infections are chronic in nature and elevated IgG4 levels are associated with length of exposure. To examine how structure, localization and dynamics of exposure of a protein to the immune system can affect antibody isotype expression, specific antibody levels against two Schistosoma mansoni recombinant cathepsin molecules were determined in S. mansoni-infected individuals. Cathepsin B (rCatB, secreted in the gut) and cathepsin L (rCatL, localized in the reproductive structures) were used to determine IgG1 reactivity, as a measure of the stimulation of the immune response, and the switch to IgG4 as an indicator of the dynamics and rate of presentation to the immune system. Sera from three groups of S. mansoni-infected patients were used: individuals with life-long exposure in an endemic area in Burundi, a group from a recent endemic focus in Senegal, and of acutely infected European travellers. We report for the first time the ability of rCatL to trigger an immune response and show distinct antibody isotype reactivity between rCatB versus rCatL. Patients harbouring long-term chronic infections had elevated levels of IgG4 to both antigen, whereas individuals infected for less than four years had high IgG4 to rCatB but not to rCatL. Acutely infected travellers developed IgG1 to rCatB only. Our results demonstrate that an immune response is mounted more rapidly against a cathepsin molecule secreted in the gut of the worm than against an internally localized cathepsin.

Interleukin-12 suppresses immunoglobulin E production but enhances immunoglobulin G4 production by human peripheral blood mononuclear cells.

The effect of interleukin-12 (IL-12) on human immunoglobulin G4 (IgG4) and IgE production was examined with cells derived from filarial patients and European controls. IL-12 inhibited IgE release but enhanced IgG4 production in cultures of peripheral blood mononuclear cells stimulated with anti-CD2 plus IL-2. When purified T- and B-cell cocultures were examined, IL-12 again markedly enhanced IgG4, whereas IgE production was no longer inhibited.

Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae.

The possibility of preventing pregnancy-induced hypertension (PIH) and pre-eclampsia in primigravidae by suppressing production of thromboxane A2 with low-dose aspirin was investigated in a randomised, placebo-controlled, double-blind trial. 46 normotensive women at 28 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because of an increased blood-pressure response to intravenously infused angiotensin II, were studied. 23 women received 60 mg aspirin daily, and the same number received matching placebo until delivery. In the placebo group PIH, pre-eclampsia, and eclampsia developed in 4, 7, and 1 cases, respectively, whereas only 2 women in the aspirin group had mild PIH. There were no adverse effects of treatment in mothers or infants. Low-dose aspirin may restore prostacyclin/thromboxane imbalance, previously suggested as an important aetiological factor in PIH and pre-eclampsia.