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Anticardiolipin (aCL) antibodies have been described in diverse clinical situations, linked to the risk of thrombosis in different vascular locations. They have been rarely studied in renal diseases, and occasionally they have been associated with glomerular thrombosis. We analyzed the incidence of aCL (isotypes IgG, IgA, and IgM) in samples, taken during the acute phase of the disease, from 27 well-documented patients having acute poststreptococcal glomerulonephritis. Twelve cases were positive on IgG testing, 1 case on IgA testing only, and no one was positive on IgM testing. A serological follow-up was performed with a second sample taken about 7 months later, for the patients initially positive on IgG testing showing persistence in 9. Clinical variables during the acute phase and after a follow-up period of 25 (range 6-89) months were analyzed for possible associations with the presence of these antibodies, but non was significantly related. Renal histopathological investigation did not reveal particular findings in the aCL-positive patients, and glomerular thrombosis was not found in any case. In addition, serum samples from 12 streptococcal impetigo patients without renal involvement were analyzed, showing similar incidence (4 positive on IgG testing, 1 of them positive on IgM testing as well, and no one positive on IgA testing) and titers of aCL antibodies. We conclude that the presence of aCL antibodies in acute poststreptococcal glomerulonephritis may be a marginal immunological phenomenon unrelated to the glomerular disease, triggered by the streptococcal infection.

Anticardiolipin (aCL) antibodies have been associated with thrombocytopenia, hemolytic anemia and an increased risk of thrombosis in different vascular locations, even in the absence of lupus. The classic hemolytic-uremic syndrome is a postinfectious acute renal failure characterized by hemolytic anemia, thrombocytopenia and the presence of widespread glomerular thrombosis in the kidney, with pathogenic mechanisms that remain to be identified. In order to establish the frequency of aCL antibodies in this syndrome and to identify a possible role in the pathogenesis and clinical manifestations, 17 patients were studied during the reactant phase of the disease looking for an association between the presence of aCL antibodies (isotypes IgG, IgA and IgM) and the main clinical variables of the syndrome. In 8 patients IgG aCL was present, 2 patients had IgM aCL, and 1 had IgA antibodies on the solid-phase ELISA aCL assays, but no association could be demonstrated with the clinical variables studied. Although it might correspond to an epiphenomenon related to the triggering intestinal infection, a pathogenic role cannot be discarded and additional studies should be performed.

Sera from 210 patients with Acute Poststreptococcal Glomerulonephritis (APSGN) and 14 patients with streptococcal impetigo without glomerular disease were tested for the presence of IgG-ANCA using an indirect immunofluorescence assay (IIF) on ethanol fixed normal human neutrophils. In the group of nephritic patients, ANCA were detected by IIF in 9% (18 out of 210 cases) in an atypical diffuse cytoplasmic pattern (a-ANCA) in 14 cases and in a (p-ANCA) perinuclear staining in the remaining 4 cases. Longitudinal studies performed on six IIF positive patients, showed persistence of the phenomenon for up to six months, without relationship with activity of disease. No patient with streptococcal impetigo showed positivity on the IIF assay. Positive sera were analyzed on ELISA plates for their IgG reactivity against specific purified ANCA antigens: Proteinase-3 (PR3), Myeloperoxidase (MPO). Cathepsin-G and Bactericidal/Permeability Increasing Protein (BPI). Anti-MPO antibodies were present in 4 cases (3 a-ANCA and 1 p-ANCA). No reactivity was identified against PR-3, BPI and Catepsin-G in any of the samples. The presence of ANCA was significantly associated with a more severe glomerular disease as assessed by the serum creatinine and the crescents formation. Further studies are required to identify other antigenic specificities of these autoantibodies. Their absence in the streptococcal impetigo control group might suggest that their presence in APSGN could play some pathogenic role in kidney disease.

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG, and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability-increasing protein (BPI), a recently-characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI & FEV1: r = -0.508, p < 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (n = 6) than in those without (p < 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.

We studied the presence of antineutrophil cytoplasmic antibodies in 16 patients with idiopathic ulcerative colitis, using an indirect immunofluorescence technique and specific ELISA for myeloperoxidase and proteinase 3. Twelve patients had an active disease and in ten, antineutrophil cytoplasmic antibodies were positive, with a predominantly perinuclear distribution and without specificity for myeliperoxidase or proteinase 3. These antibodies were negative in the four patients with inactive disease. It is concluded that antineutrophil cytoplasmic antibodies could be serologic indicators of disease activity in patients with ulcerative colitis.

Mean platelet survival time in patients with acute poststreptococcal glomerulonephritis (APSGN) is reduced to 50-60% of the control values, and glomerular deposits of platelet factor 4 are found in these patients. In order to investigate further systemic platelet changes of pathogenic, clinical or prognostic significance, we measured the platelet serotonin (5-HT) content and the blood platelet counts during the 1st week of the disease in 27 patients with APSGN. Platelet 5-HT was significantly reduced in patients with APSGN as compared with patients with impetigo without glomerular involvement (785 +/- 54 vs. 1,329 +/- 94 ng 5-HT/10(9) platelets; p < 0.001). Similarly, the mean blood platelet count was reduced to 247 +/- 16 x 10(3) as compared with 303 +/- 14 x 10(3) in the controls (p < 0.05). Thirteen (48%) of these patients had individual values of platelet 5-HT lower than the 95% confidence interval calculated in the control group. No significant correlation was observed between the concentration of 5-HT and either the severity of the disease judged by the amount of urinary protein excretion and the serum creatinine value or the presence of circulating immune complexes. Significant correction of the platelet 5-HT content (to 1,180 +/- 111 ng/10(9) platelets; p < 0.01) and of the platelet counts (to 309 +/- 21 x 10(3); p < 0.01) were observed in the longitudinal study at least 2 weeks later. Platelet activation, with secretion of granular content and increased consumption, may explain these findings. Additionally, the reduced mean age of the circulating platelets could contribute to their decreased 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineutrophil cytoplasmic autoantibodies (ANCA), are serologic markers of disease in rapidly progressive glomerulonephritis without immune deposits (pauci-immune) and vasculitis, and could play a pathogenic role in these diseases. We communicate 5 patients with pauci-immune rapidly progressive glomerulonephritis; four of them in the evolution of necrotizing systemic vasculitis (Wegener's granulomatosis and microscopic polyarteritis) and one case with lesions limited to the kidney. All of them were associated with the presence of ANCA. The immunofluorescence pattern (cytoplasmic and perinuclear) and the antigenic specificity of ELISA assay, [antiproteinase-3 (PR-3) and antimyeloperoxidase (MOP)], are useful laboratory tools for the diagnosis and clinical management of these patients.

Sera from 210 patients with APSGN, were tested for the presence of ANCA (IgG-isotype). Indirect immunofluorescence (IF) on ethanol fixed human PMNs was used, and for those positive sera, ELISA kits for PR3 (Proteinase 3) and MPO (Myeloperoxidase) was performed. ANCA were detected in 9% (18 out of 210 cases) in a predominantly diffuse cytoplasmic staining pattern in 14 cases (77%), and in a perinuclear pattern in the remaining 4 cases (22%). Anti-MPO was found in 4 cases (C-ANCA 3; P-ANCA 1) and anti-PR3 was always negative. The presence of ANCA was significantly associated with a more severe glomerular disease as assessed by the serum creatinine value and the crescents formation. Longitudinal studies performed in 11 cases have shown that raised levels of these autoantibodies may persist for at least six months, without relationship with disease activity. Further studies are required to dilucidate the specificity of these autoantibodies, and if its presence is either an epiphenomenon of the heterogeneous humoral immune response in streptococcal infection, or they play some pathogenic role in APSGN.

A patient with idiopathic membranous nephropathy and nephrotic syndrome developed inappropriately high red blood cell counts, unrelated to the level of serum creatinine. This unusual event could be explained by an overstimulation of the erythropoietin hormone due to hypoperfusion associated to the nephrotic syndrome.

Since platelet factor 4 (PF4), a cationic (pI 7.6) platelet secretory protein, binds avidly to glomerular polyanions both in vitro and in vivo, and is implicated in neutrophil chemotaxis, we studied by indirect immunofluorescence microscopy the presence of PF4 deposits in glomeruli of patients with poststreptococcal nephritis (APSGN). Goat antihuman PF4 serum was used as primary antibody and fluorescein-conjugated IgG fraction of rabbit antigoat IgG as second antibody. Controls consisted of nonimmune goat serum or anti-PF4 serum preabsorbed with human PF4, as primary antibodies. Glomerular deposits of PF4 were demonstrated in renal tissues obtained by biopsy in 14 of 20 patients studied; the deposits were particularly intense in 9 patients. PF4 was bound to the mesangium and to the capillary walls. There was a significant positive correlation between intraglomerular deposits of PF4 and the levels of proteinuria (p = 0.024). These findings provide further evidence for a role of platelets in the pathogenesis of APSGN and suggest that PF4 may contribute to alter the glomerular permeability in this disease.

The Fc-receptor function of the mononuclear phagocyte system (MPS) was examined in 41 children and adult patients, by measuring the clearance of IgG-sensitized, 51Cr-labeled erythrocytes. The Fc-receptor-mediated clearance observed in patients (mean +/- SE) was not significantly different as compared to the control group of similar age distribution. However, the immune clearance time was significantly age-correlated in both groups (acute poststreptococcal glomerulonephritis, APSGN, r = 0.39, p less than 0.05; control r = 0.63, p less than 0.01). The magnitude of the Fc-specific immune clearance and the serum creatinine were also significantly correlated (r = 0.59; p less than 0.01). Circulating immune complexes (as measured by the C1q and conglutinin ELISA) did not correlate with immune clearance, which remained stable in longitudinal studies. Age-related changes in MPS Fc-receptor function could explain, at least in part, prognostic differences between children and adult patients with APSGN.

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.

In an attempt to study further the possible participation of platelets in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), we studied the platelet survival time, as an index of platelet activation, in 22 patients with APSGN. Mean platelet survival time was computed from the disappearance of radioactivity from blood, sampled serially after injection of autologous 51Cr-labelled platelets. C1q solid phase ELISA and conglutinin (K) solid phase ELISA were used to measure the serum levels of immune complexes. The platelet survival time in APSGN patients was 113 +/- 10 h vs 197 +/- 10 h in the control group (p less than 0.001); 68% of the patients had a shortened platelet survival, lower than 95% confidence limit. There was a significant increase in the platelet survival in the six patients that were studied after recovery from acute nephritic syndrome. There was no significant association between the mean platelet times survival and CICs (circulating immune complexes). Similarly, no significant correlation was found between the mean platelet lifespan and the severity of the glomerular disease, as assessed by the serum creatinine level and the proteinuria. These results support evidence of platelet activation and consumption in APSGN and we suggest that this activation occurs in the glomeruli capillary wall, due to platelet-vascular wall interaction.

A 28 year old man developed acute cellular rejection after renal transplantation. He received double i.v. pulses of methylprednisolone. A spontaneous rupture of the right external iliac artery occurred. Histology revealed the presence of aspergillosis. A review of the literature is included.

In an attempt to further study the possible contribution of circulating immune complexes (CIC) in the pathogenesis of acute poststreptococcal glomerulonephritis, 61 patients with APSGN were studied during the first three weeks of the disease, and 13 patients with noncomplicated streptococcal impetigo as a control group. C1q solid phase ELISA and Conglutinin (K) solid phase ELISA were used to measure the levels of immune complexes. The incidence of CIC in a single serum sample from patients with APSGN was 48%. Elevated levels of immune complexes were found in 46% of the patients with streptococcal impetigo. The absolute levels of CIC were comparable in both groups of patients. No correlation was found among the presence of CIC and the clinical, immunoserological or pathological findings of the disease. Our results do not support the hypothesis that trapping of the circulating immune complexes play an important role on the renal injury poststreptococcal infection. Instead, we suggest that CIC are an epiphenomena present in APSGN, and may represent rather a systemic inflammatory immune response in patients with group A streptococcal infection.

51 patients, mainly adults, with idiopathic membranous glomerulonephropathy were studied to evaluate their clinical course and long-term prognosis. Glomerular lesions were classified into four groups, according to Ehrenreich and Churg: 5 had type I, 19 type II, 20 type III and 7 type IV lesions. The onset was marked by a nephrotic syndrome in 47 patients (92%). Hypertension was present in 41% and the serum creatinine was over 2 mg/dl in 17%. During the follow-up period (mean 42 months) clinical remission occurred in 7 cases, clinical improvement in 4 patients, renal insufficiency in 11 patients (with end-stage renal failure in 10 and the condition remained unchanged in 29 cases. The actuarial life-table survival at 5 and 15 years was 80% and 56% respectively, excluded the 5 patients with renal vein thrombosis. The retrospective comparison in patients who did (n = 29) or did not (n = 22) receive corticosteroids, shows a favorable outcome of treated patients. Poor prognostic indicators were: impaired renal function at time of diagnosis, and advanced histologic staging.