RESUMO
OBJECTIVE: To evaluate the relevance of antibodies to ribosomal P proteins (anti-P antibodies) in discriminating histopathologic patterns of lupus nephritis. METHODS: The study group comprised 81 consecutive patients with systemic lupus erythematosus who underwent renal biopsy and for whom frozen serum was available at the time of biopsy. All biopsy specimens were reviewed in a blinded manner, according to the 2004 criteria of the International Society of Nephrology and the Renal Pathology Society. Anti-P antibodies were detected by enzyme-linked immunosorbent assay (ELISA)/immunoblot analysis, and anti-double-stranded DNA (anti-dsDNA) was detected by indirect immunofluorescence/ELISA. RESULTS: Anti-P antibodies were detected in 18 patients (22%). The demographic and clinical features of patients with and those without anti-P antibodies were similar. Remarkably, analyses of biopsy specimens revealed that the frequency of anti-P antibodies in patients with class V lupus nephritis was higher than the frequency among patients with other classes of renal disease (72% versus 28%; P = 0.005). Accordingly, anti-P antibody-positive patients had a higher mean (+/-SD) proteinuria level compared with anti-P antibody-negative patients (6.4 +/- 4.8 versus 4.7 +/- 3.9 gm/dl; P = 0.046). Renal function was preserved in 6 of 7 patients who had both isolated anti-P antibodies and class V lupus nephritis. In contrast, anti-dsDNA was associated with proliferative-class lupus nephritis (P = 0.050) and higher creatinine levels (P = 0.014). Furthermore, 7 of 9 patients with isolated anti-P antibodies had class V lupus nephritis, and, more importantly, 5 of these 7 patients (71%) displayed a pure membranous pattern. Conversely, a tendency toward the predominance of class V lupus nephritis (67%) with concomitant proliferative lesions was observed when anti-P antibody was associated with anti-dsDNA. CONCLUSION: Our data introduce anti-P antibody as a novel serologic marker for membranous lupus nephritis and support the notion that the presence of isolated anti-P antibodies may discriminate patients with pure class V lupus nephritis, whereas the simultaneous presence of anti-dsDNA antibodies suggests class V disease with concomitant proliferative lesions.
Assuntos
Autoanticorpos/sangue , Glomerulonefrite Membranosa/sangue , Nefrite Lúpica/sangue , Proteínas Ribossômicas/imunologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , MasculinoRESUMO
The morphological changes in both insulin-dependent and non-insulin-dependent diabetes mellitus (IDDM and NIDDM) are indistinguishable. The earliest pathological changes are enlarged glomeruli due to hypertrophy seen mainly in IDDM patients. There is also an increase in total volume of both basement membrane (BM) and capillary lumen. A second peak of glomerular hypertrophy occurs late in the disease when overt pathological changes are established. At this, many glomeruli are comprised and the open, functioning glomerulii will show a three-fold increase in size. The pathognomonic change in diabetic nephropathy is nodular glomerulosclerosis or nodular intercapillary glomerulosclerosis (Kimmelstiel-Wilson lesion) which is characterised by enlargement of mesangium due to increase in mesangial matrix. This is associated with diffuse thickening of the capillary wall which is due to increased BM material. A diffuse lesion may be considered specific after ruling out all the other causes of thickened BM, i.e. immune-complex glomerulonephritis, anti-glomerular basement membrane antibody disease, etc. The exudative and capsular drop lesions are not specific for diabetes mellitus but can be considered to be highly suggestive lesions. There is hyaline arteriolosclerosis, involving both afferent and efferent arterioles. The only pathognomonic tubular lesion (Armanni-Ebstein lesion) is a rare finding, and is found in the straight portion of the proximal convoluted tubules in which tubular cells contain glycogen. The patients with the nephropathic syndrome may show lipid-filled proximal tubules. In the late stages, there are non-specific atrophic changes with thickening of the basement membrane. There are no specific gross features of the kidney in diabetes mellitus. It may be enlarged, normal or granular contracted. The subscapular surface may either be finely or coarsely granular with focal depressed scars. The cut surface may show thinning of the cortex, loss of the corticomedullary junction and prominent blood vessels. Papillary necrosis is uncommon (AU)
Assuntos
Humanos , Diabetes Mellitus/patologia , Circulação Renal , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Glomerulonefrite Membranosa/sangue , Hipertrofia , Nefropatias Diabéticas , Mesângio Glomerular , Complexo Antígeno-Anticorpo , Arteriosclerose , Membrana Basal , Necrose Papilar RenalRESUMO
We describe a child with circulating anti-epithelial cell antibodies, autoimmune enteropathy with intestinal villous atrophy, and membranous glomerulonephritis. The patient had persistent diarrhea at 6 months of age, and a small bowel biopsy showed active enteritis, villous atrophy, and crypt hyperplasia. When the patient was, 10 months of age, nephrotic syndrome developed because of membranous glomerulonephritis. Results of tests for circulating immune complexes were negative. Indirect immunofluorescence studies revealed a circulating antibody directed against renal epithelial cells. Circulating antibodies directed against normal small intestine epithelial cells were also detected by the immunoperoxidase technique. Western blot and immunoprecipitation identified a 55-kd antigen, in both small bowel and kidney, that reacted with an antibody in the patient's serum. High-dose prednisone therapy induced a clinical remission, resolution of the small bowel injury, and diminished serum anti-epithelial cell antibodies; after dose reduction, clinical relapse occurred with villous atrophy and reappearance of anti-epithelial cell antibodies. When the patient was 45 months of age, persistent diarrhea recurred despite intravenous administration of corticosteroids, cyclosporine, and total parenteral nutrition. Autoantibodies to a 55-kd epithelial cell protein are temporally related to the development of enteropathy and nephropathy. Study of similar patients is needed to determine the role of such antibodies in this disorder.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Glomerulonefrite Membranosa/imunologia , Enteropatias/imunologia , Intestino Delgado/patologia , Atrofia , Doenças Autoimunes/sangue , Doenças Autoimunes/tratamento farmacológico , Células Epiteliais , Epitélio/imunologia , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Imunoglobulinas/análise , Lactente , Enteropatias/sangue , Enteropatias/tratamento farmacológico , Intestino Delgado/imunologia , Masculino , Prednisona/uso terapêuticoRESUMO
Familial idiopathic membranous nephropathy, an immune-complex-associated glomerulopathy, has not been previously reported in father and son, despite its striking immunogenetic correlation, especially with HLA-DR3. As a dysfunction of the monocyte-phagocyte system (MPS), it has been observed linked to DR3 antigen, so we studied the MPS Fc receptor function in a father and his son with a histologically proven membranous nephropathy, associated with the haplotype A9-B35-DR3-DQw2. The Fc receptor function of the MPS was examined by measuring the clearance of IgG-sensitized, 51Cr-labeled erythrocytes and by measuring the ability of isolated monocytes to ingest autologous red blood cells coated with IgG anti-Rh (D) antibody. Immune clearance and in vitro phagocytosis was normal in both patients and not related to their levels of immune complexes (as measured by ELISA C1q and Conglutinin solid-phase binding assay). This report suggest that genetic factors may play an important role in the development of membranous nephropathy, and it seems not to be related to a dysfunction of MPS as measured by these tests.
Assuntos
Glomerulonefrite Membranosa/imunologia , Antígeno HLA-DR3/imunologia , Monócitos/ultraestrutura , Fagócitos/ultraestrutura , Receptores Fc/fisiologia , Adolescente , Adulto , Complexo Antígeno-Anticorpo/sangue , Ensaio de Imunoadsorção Enzimática , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/fisiopatologia , Humanos , Masculino , Monócitos/fisiologia , Fagócitos/fisiologia , Fagocitose/fisiologiaRESUMO
The purpose of this retrospective study was to study the incidence of idiopathic and secondary forms of membranous nephropathy in our institution, its clinical course and progression to chronic renal failure, and the risk factors associated with it. Two hundred fourteen (16%) of the 1,287 renal biopsies obtained between 1962 and 1988 were primary glomerular diseases and 28 of this 214 (13%) were idiopathic membranous nephropathy. On the other hand 59 of 1,287 biopsies were membranous nephropathy of whom 28 were idiopathic, 27 secondary to systemic lupus erythematosus, 2 due to drugs, one associated with rheumatoid arthritis, and one more with breast cancer. The clinical picture was: nephrotic syndrome in 84%, hypertension in 15%, non-nephrotic proteinuria in 14%, chronic renal failure in 8.4%, and renal vein thrombosis in 6.3%. In the idiopathic group 75% of the patients were male while in the lupus group 85% were female. For the analysis of progression to chronic renal failure we excluded 5 patients with renal failure when the biopsy was taken, 2 because the nephropathy was due to drugs, one associated with breast cancer, and nine were within the first year of follow-up. Thus, for this analysis the group consisted of 22 patients with idiopathic form and 20 with systemic lupus erythematosus. The idiopathic and lupus groups were similar except for a lower serum albumin in the former. The progression to renal failure was seen in 9 patients: six in the idiopathic group and the other 3 in the lupus group; this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)