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Background: The discovery of indoleamine 2,3-dioxygenase (IDO) as a modulator for the maintenance of fetomaternal immuno-privileged state has been heralded as a significant step in further defining the role of IDO in immunobiology. IDO is an IFN-inducible, intracellular enzyme that catalyzes the initial and rate-limiting step in the degradation of the essential amino acid, tryptophan. It has been suggested that IDO has the capacity to regulate the immune system via two discrete mechanisms; firstly the deprivation of tryptophan, which is essential for T cell proliferation and via the cytotoxic effects of tryptophan metabolites on TH1 cell survival. Methods: The sources of information used to prepare the paper are published work on Pubmed/Medline. In this review, we examine the therapeutic role of modulating IDO activity a variety of disease states including tumour tolerance, chronic infection, transplant rejection, autoimmunity and asthma. We propose that IDO represents a novel therapeutic target for the treatment of these diseases. We also explore the diverse strategies which are being employed, either to augment or to inhibit IDO activity in order to modify various disease processes. The limitations associated with these strategies are also scrutinized.

Background: A recent incident, the halting of a Phase I/II trial utilising an adeno-associated vector, highlights the fact that there are more hurdles to overcome prior to a full realisation of gene therapy in the clinical arena. Methods: The sources of information used to prepare the paper were obtained through published work on Pubmed/Medline and materials published on the US/UK governmental agency websites. Results/conclusion: Over the years, two fatal incidents associated with viral vector usage have been reported. Viral vectors used as carriers for gene therapy have failed in safety trials on two occasions. Also, the human immune response and the oncogenic property of the vectors have restricted the advancement of gene therapy as a therapeutic tool. Nonetheless, gene therapy has now progressed from its infancy ‘proof of concept’ stage, to the next stage in which we try to overcome the problems associated with therapeutic application. However, this progression has been slow as more and more setbacks have occurred. This calls for a new perspective and radical thinking about future vector development.

The simultaneous occurrence of postinfectious glomerulonephritis and thrombotic microangiopathy is described in renal biopsy specimens from three patients. Each presented with diverse manifestations: two patients had hypertension and acute renal failure, and in the third, it was unclear whether an atypical postinfectious glomerulonephritis or an atypical thrombotic microangiopathy was present. All biopsy specimens disclosed a combination of irregular granular complement and immunoglobulin deposits in mesangial regions and capillary walls along with fibrin in a linear pattern in capillary walls by immunofluorescence. Light microscopy showed diffuse hypercellularity in some glomeruli, endothelial cell swelling, luminal thrombi and mesangiolysis in others, and both types of changes in a third group. Ultrastructurally, subepithelial hump-shaped deposits coexisted with widened and lucent subendothelial spaces. Possible pathogenic mechanisms for the synchronous lesions include endothelial injury, perhaps triggered by infection and immunologic tissue damage. (Am J Kidney Dis 1998 Mar;31(3):513-20)