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Mycophenolate mofetil (MMF) initially found widespread use in the immunoprophylaxis of rejection in organ transplantation. It has subsequently been used in lupus glomerulonephritis, where early studies have shown it to be effective in induction and maintenance therapy. The randomized studies have mostly studied small groups of patients and their conclusions do need to be confirmed in larger studies. MMF has also been used in small numbers of patients in a variety of nonlupus glomerulopathies, which have different underlying immunopathology as well as clinical course, including IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, hepatitis-C-associated glomerulonephritis and even Goodpasture's syndrome. In this article, we discuss its use in such nonlupus glomerular diseases.

Cytomegalovirus (CMV) is usually a complication of renal/solid organ or bone marrow transplantation. We describe three cases of severe CMV in the context of vasculitis immunosuppression.

Hepatitis C virus (HCV) seroconversion was detected by routine screening in a haemodialysis patient, Patient 1. Serological investigations were undertaken over the following 3 months to determine if further transmission to other patients on the unit had occurred. No additional cases were identified. Twenty-two haemodialysis patients known to have HCV infection were investigated using molecular epidemiological methods to determine if transmission between patients had occurred. HCV viraemia was demonstrated by polymerase chain reaction in 19 of 22 patients (86%). Genotyping showed that eight patients were infected with genotype 1, three with genotype 3 and eight, including Patient 1, with genotype 2. Phylogenetic analysis of viral sequences from the eight patients with genotype 2 revealed three, including Patient 1,with a novel subtype of HCV type 2, and revealed close similarity between viral sequences from patient 1 and those from one other patient, suggesting transmission. This was consistent with haemodialysis histories. Among other patients with genotype 2, there were two with subtype 2a and three others with three separate novel subtypes, as yet undesignated. With the exception of patient 1, all patients infected with novel subtypes were of Afro-Caribbean origin. The HCV prevalence among patients on the haemodialysis unit was high (14%), which may reflect the ethnicity of our haemodialysis population. This case emphasises the risk of nosocomial transmission and the importance of infection control procedures on haemodialysis units, and highlights the usefulness of molecular epidemiological techniques for the investigation of outbreaks of HCV infection., (Copyright 1999 Wiley-Liss, Inc.)

We report the case of a 66-year-old female who over an 18-month period developed severe, disabling scleromyxoedema with pulmonary fibrosis. Treatment with oral prednisolone and melphalan had failed to prevent disease progression. Treatment with a 5-day course of plasma exchange, intravenous cyclophosphamide (500 mg) and methyl-prednisolone (1 g on 3 consecutive days) was unfortunately followed by the development of thrombotic thrombocytopaenic purpura (TTP). After 17 extra plasma exchanges, she recovered and there has been a dramatic improvement in her skin signs. We postulate that the extra plasma exchanges which she received as a consequence of developing TTP have contributed to this result. To our knowledge, TTP has never been associated with scleromyxoedema, but it is likely to be a coincidence in this case.

The murine monoclonal antibody OKT3 is the best known of the anti-CD3 antibodies used for the prevention and treatment of renal allograft rejection. Use of this antibody is associated with improved graft outcome but it has a number of adverse effects thought to result from the massive release of pro-inflammatory cytokines. It has been postulated that OKT3 causes cytokine release because of cross-linking of CD3 molecules on the cell surface by bivalent anti-CD3 antibodies, such as OKT3, and the simultaneous binding of the Fc regions of these monoclonal antibodies to Fc receptors on other cells resulting in cell activation. Monovalent antibodies directed against the CD3 antigen should not, in theory, cause cell activation and cytokine release by this postulated mechanism. This study details the use of a monovalent anti-CD3 monoclonal antibody in the treatment of allograft rejection in five renal transplant recipients and documents the degree of TNF, IFN-g and IL6 release generated after antibody injection. Monovalent anti-CD3 monoclonal antibody reversed the rejection episode for which it was used and was well tolerated in all patients. TNF, IFN-g and IL6 measurement showed that little pro-inflammatory cytokine release occurred after this drug. It is likely that the relative lack of side-effects of monovalent anti-CD3 reflects the blunted release of pro-inflammatory cytokines. Monovalent anti-CD3 monoclonal antibody may be a useful addition to the reagents available to treat allograft rejection.

Activated T cells bearing receptors for interleukin 2 (IL-2) play an important role in immunity and in immunopathological processes such as allograft rejection. In order to investigate the presence of activated T cells in lymphocytic infiltrates in transplanted kidneys, we investigated the uptake and retention of radioactivity after an intravenous injection of radioiodinated IL-2 in experimentally transplanted rats. IL-2 was enzyme radiolabelled with 123iodine using a glucose oxidase/lactoperoxidase method and shown to retain specific binding on an IL-2 receptor positive cell line, C58E6. To examine the kinetics of 123iodine-interleukin 2 (123I-IL-2) uptake in vivo, animals that had been transplanted five days previously with allogeneic or syngeneic grafts were injected with 123I-IL-2 and then imaged using an external gamma camera. Radioactivity was measured at time points up to 240 min after intravenous injection of 123I-IL-2. Four groups of animals were examined: allogeneic grafts (n = 7); syngeneic grafts (n = 6); ischaemic native kidneys (n = 5) all following injection with 123I-IL-2; and allogeneic transplants (n = 5) after injection of 123I-lactalbumin, an irrelevant molecule of similar molecular weight to IL-2. The peak radioactivity after injection was measured and the amount of radioactivity retained in the graft at increasing time intervals after injection was expressed as a function of initial peak radioactivity. At four hours after injection of 123I-IL-2, mean retention of activity by rejecting grafts was 77(+/- 2.68)% of peak activity, compared to 45(+/- 6.38)% in syngeneic controls (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)