A 31-year-old Malay female presented with nephrotic syndrome without renal impairment. Renal biopsy features were in keeping with immunotactoid glomerulopathy (ITG). Non-Congophilic deposits were seen causing thickening of the glomerular capillary basement membrane with segmental accentuation, and widening of the mesangium. Immunofluorescence examination showed moderate amounts of IgG and C3 in the glomerular capillary walls with some in the mesangium. Ultrastructurally, 20-nm thick fibrils with microtubular organisation were present predominantly in the subendothelial region with similar fibrils in the mesangium. Although immunotactoid glomerulopathy and fibrillary glomerulonephritis (FG) have been recognised as entities with extracellular fibrillary material in the kidney, to date much remains to be clarified regarding these 2 conditions. While the renal biopsy findings in this patient are consistent with ITG, her clinical presentation is unlike that of usual ITG in that she is of a much younger age and has no associated haemopoietic disorder. Response to initial treatment of 8 weeks of prednisolone therapy was poor.
From a total of 163 renal biopsies there were 12 cases (9.1%) of IgA nephropathy. All of them presented with symptomatic or asymptomatic proteinuria and/or haematuria. The pattern of disease here generally conforms to reports elsewhere. However in contrast it appears to be common in both sexes and the clinical course tends to be more severe In males. The absence of IgG In the glomeruli on immunoffourescence was an unexpected finding. The presence of hypertension, renal insufficiency and glomerulo·interstitial scarring seem to indicate poorer prognosis. There is no known effective treatment.
Two forms of abnormal fibrillary protein deposition are considered: amyloidosis and fibrillary (immunotactoid) glomerulonephritis. Amyloid is characterised by an antiparallel, beta-pleated configuration which imparts to it a unique apple-green birefringence after Congo red staining. Inspite of its fairly constant physical properties, the chemical composition of amyloid fibrils is amazingly diverse, encomposing AA protein, light chain fragments, transthyretin, procalcitonin, islet amyloid polypeptide, atrial natriuretic peptides, beta-amyloid protein, beta-2-microglobulin, cystatin C, gelsolin, apolipoprotein A1, lyzozyme and their mutant variants. Amyloid P component and heparan sulphate proteoglycan are ubiquitous non-fibrillary amyloid components which have significant roles in the amyloidogenetic process, as do also precursor fibril proteins. Different amyloid fibril proteins relate to different amyloidosis syndromes and different histological patterns, and provide the basis for new diagnostic approaches to this disorder. Glomerular deposits in fibrillary glomerulonephritis (FGN), although often mistaken for amyloid, differ from it in its negative Congophilia, wider fibril width and highly organised, microtubular-tactoidal appearance ultrastructurally. FGN is essentially a primary glomerulopathy resulting in progressive renal failure. Despite certain differences, intriguing similarities between both entities of fibrillary deposition pose a challenge to researchers as to the mechanisms of abnormal protein crystallization and fibril formation in tissues.
Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a Staphylococcus aureus peptide, homologous to an immunodominant MPO T-cell epitope (MPO409-428), can induce anti-MPO autoimmunity. The peptide (6PGD391-410) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some S. aureus strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD391-410, or with S. aureus containing a plasmid expressing 6PGD391-410, develop glomerulonephritis when MPO is deposited in glomeruli. The peptide induces anti-MPO autoreactivity in the context of three MHC class II allomorphs. Furthermore, we show that 6PGD391-410 is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD391-410 antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.