Luis Hernando

Role of platelet-activating factor in adriamycin-induced nephropathy in rats

The effect of steroids, heparin and specific PAF-acether antagonists (BN 52021 and triazolobenzodiazepines) on proteinuria and renal histological changes induced in rats by adriamycin was studied. Adriamycin evoked a marked proteinuria that was unaffected by methylprednisolone and slightly reduced by heparin. In contrast, adriamycin-injected rats treated with PAF-acether antagonists had a low proteinuria, if any, and no ultrastructural glomerular alterations. These data suggest that PAF-acether could play a major role in the occurrence of proteinuria and that PAF-acether antagonists might provide a new therapeutic approach in certain human nephropathies.

Immunological abnormalities in healthy relatives of patients with IgA nephropathy

Patients with IgA nephropathy have elevated serum levels of polymeric IgA, probably due to an increase in their synthesis by peripheral blood mononuclear cells, and specific abnormalities in the immunoregulation of IgA. The existence of familial cases of IgA nephropathy, as well as the published association of this nephropathy with some antigens of the HLA system, decided us to test the hypothesis that some of these alterations might be genetically controlled. For this reason we studied some of these immunological assays in 25 first-degree relatives of 7 patients with IgA nephropathy and 22 control subjects matched for age and sex. An abnormal immunological assay was found in at least 1 relative of all families examined. Thus, 16 of 25 relatives had a significant increase in the percentage of polymeric IgA-producing cells after 7 days of culture in the presence of pokeweed mitogen. Some derangement in the concanavalin A generation of specific IgA suppressor cells was found in 11 out of 25 relatives. These results are, though in lower frequency, similar to those seen in patients and suggest that the IgA-immunological abnormalities observed are genetic markers, even if they cannot by themselves explain the pathogenesis of the IgA nephropathy. The absence of IgA immune complexes seen in relatives as well as their high prevalence in patients suggest that in predisposed subjects other factors (genetic or not) are required for the development of IgA nephropathy.

Evidence of an immediate hypersensitivity mechanism in systemic lupus erythematosus.

In 30 patients with systemic lupus erythematosus the number of a circulating basophils was countered in different stages of activity. An inverse correlation was found between the absolute basophils count and anti-DNA antibodies and presumptive circulating immune complexes (as judged by polyethylene glycol precipitation of serum). A positive correlation was found between the absolute basophil count and C3 or C4 levels. IgE on the basophil surface was determined by radioimmunoassay in 7 patients. All of them showed a significantly higher surface IgE number. When the count of circulating basophils was roughly normal, 5 out of the 6 patients showed a positive basophil degranulation test with native DNA. These results suggest the existence of an anti-DNA specific IgE in lupus patients. Depression of the circulating basophil count may be a useful index of lupus activity.

Immunological Aspects of Renal Vascular Involvement

The majority of cases of human vasculitis are thought to be immunologically mediated. The contribution of experimental models, such as acute serum sickness of rabbits, Arthus reaction (including Arthus nephritis) and virus-induced vasculitis, to the knowledge of the problem is reviewed, emphasizing the mechanisms involved in the deposition of immune complexes and mediator systems of vascular injury.

New Therapeutic Approach to IgA Mesangial Glomerulonephritis (Berger’s Disease)

In mesangial IgA glomerulonephritis deterioration of renal function is not uncommon, occurring in about 20% of patients after several years. In this paper we present preliminary results of a therapeutic trial with phenytoin in thirty-three patients affected by this nephropathy. Up to 1 year of follow-up no significant changes in renal function, proteinuria or haematuria were seen. A significant decrease in serum IgA and a normalization of the high polymeric IgA levels frequently found in these patients, were observed at this time. Of seven patients rebiopsied, markedly reduced IgA mesangial deposits were seen in one and disappearance in the other, by immunofluorescence and by electron microscopy.