IMMUNOGLOBULIN-A AND THE PATHOGENESIS OF SCHISTOSOMAL GLOMERULOPATHY

Several observations suggest that the evolution of schistosomal glomer ulopathy into clinically overt and progressive disease may involve pat hogenetic mechanisms other than simple glomerular deposition of parasi tic antigens. In a previous study, IgA was suggested to be a mediator of late glomerular lesions in this disease. This issue is further addr essed in this work. The stud includes 32 patients with hepatosplenic s chistosomiasis, of whom 16 had overt glomerular involvement, along wit h four control groups: (a) 15 healthy volunteers: (b) 15 patients with simple intestinal mansoniasis: (c) 17 patients with non-schistosomal chronic liver disease, and (d) 21 subjects with primary nephrotic synd rome not associated with schistosomiasis. Routine assessment was done for all subjects including confirmatory tests for schistosomal infecti on, liver and renal function tests, hepatitis viral markers and abdomi nal ultrasonography. The total serum concentrations of IgG. IgM, IgA w ere measured, as well as their respective circulating immune complexes , rheumatoid factors, anti-gliadin- and anti-DNA-antibodies. Liver and renal biopsies were obtained from the relevant groups and studied by light microscopy. Renal biopsies were also examined by immunofluoresce nce. Patients with simple intestinal schistosomiasis had a significant increase in IgM antigliadin antibodies. Those complicated with hepato splenic involvement also had a significant increase in the mean IgG an ti-gliadin antibodies, IgG rheumatoid factor and IgM anti-DNA activity . Cases further complicated by overt glomerular disease showed a disti nct IgA predominance, mainly expressed in the serum anti-gliadin antib ody pool and anti-DNA activity. This profile was essentially similar t o that observed in control cirrhotics. There was a significant increas e in the frequency of IgA glomerular deposits in rend biopsies obtaine d from patients with overt schistosomal glomerulopathy, in contrast to control nephrotics. The deposits were mainly mesangial, but were also encountered in subendothelial. subepithelial and peritubular location s. Their frequency was significantly higher with more advanced lesions as seen by light microscopy. The relevance of these data is discussed . leading to the following conclusions: (a) serum IgA-anti-gliadin and -anti-DNA antibodies, and glomerular IgA deposits are markers of sign ificant renal involvement in patients with hepatosplenic schistosomias is. (b) IgA may be involved in the pathogenesis of advanced glomerular pathology when superimposed on parasite-induced lesions. (c) There rt is a significant increase in serum auto-reactivity in hepatosplenic s chistosomiasis, which may also have pathogenic implications. (d) Incre ased production bq the inflammatory bowel lesions. impaired clearance by the fibrotic livers and probable switching of immunoglobulin synthe sis are suggested to plain the observed IgA predominance in those who develop renal complications.