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Biomedical subjects

J C Jennette

Publications and source records attributed to J C Jennette.

At least 109 records · Page 6Linked to original sources
PubMed1991

Characterization of the changes in matrix molecules at the dermoepidermal junction in lupus erythematosus.

Electron microscopy has revealed that the deposition of immunoglobulin in the skin of lupus erythematosus (LE) patients occurs on and below the basal lamina of the basement membrane (BM). The composition of the BM is now to some extent known, and antibodies have been developed against several of its individual components. In this study, we attempt to elucidate the status of some matrix molecules in the dermoepidermal junction in LE. Lesional and nonlesional skin from LE patients was examined using immunofluorescence microscopy with monoclonal and polyclonal antibodies against 6 matrix molecules. Immuno-electron microscopy using monoclonal antibodies was used to discern changes in type IV and type VII collagen. By immuno-fluorescence microscopy, type IV collagen, type VII collagen, and fibronectin were altered in lesional skin. There was a statistically significant correlation between the presence of immunoglobulin and alteration of type IV collagen and type VII collagen in lesional skin. The alterations in type IV and type VII collagens were confirmed on immuno-electron microscopy which showed fragmentation of staining of both antigenic components, particularly type IV collagen.

Antibodies, Monoclonal↗
PubMed1991

Wegener's granulomatosis, systemic vasculitis, and antineutrophil cytoplasmic autoantibodies.

Systemic vasculitis is often difficult to diagnose. The recent discovery of a new class of autoantibodies [antineutrophil cytoplasmic autoantibodies (ANCA)] provides clinicians with a serological test that strongly supports the diagnosis of the most common forms of systemic necrotizing vasculitis. The spectrum of patients with this form of vascular inflammation ranges from those with renal-limited glomerulonephritis to patients with multisystem disease, including Wegener's granulomatosis and polyarteritis nodosa.

Autoantibodies↗
PubMed1991

Cyclosporin-associated thrombotic microangiopathy: successful retreatment with cyclosporin.

This report describes a patient who developed cyclosporin-induced thrombotic microangiopathy in a renal allograft. Cyclosporin-induced thrombotic microangiopathy is considered by many as a contraindication to subsequent therapy with cyclosporin. This case is notable for successful treatment with cyclosporin following resolution of thrombotic microangiopathy in a renal allograft.

Adult↗
PubMed1990

Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network.

OBJECTIVES: To determine the spectrum of clinical manifestations in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis; to determine renal and patient survival in these patients; to compare survival among patients treated with corticosteroids alone, corticosteroids plus intravenous cyclophosphamide or corticosteroids plus oral cyclophosphamide; and to assess the correlation of disease manifestations and treatment response with ANCA subtypes and serial autoantibody titers. DESIGN: Inception cohort study; mean follow-up of 24 months. SETTING: Collaborative network of 120 university and private practice nephrologists (The Glomerular Disease Collaborative Network). PARTICIPANTS: Seventy patients with ANCA and pauci-immune necrotizing and crescentic glomerulonephritis, of whom 59 were treated with either corticosteroids alone (14 patients), corticosteroids plus oral cyclophosphamide (30 patients), or corticosteroids plus intravenous cyclophosphamide (15 patients). MAIN RESULTS: Of the 70 patients, 18 had renal-limited disease (idiopathic crescentic glomerulonephritis); 15, nonpulmonary extrarenal disease consistent with polyarteritis nodosa; and 37, pulmonary disease consistent with Wegener granulomatosis or alveolar capillaritis. There were overlapping manifestations of disease between patients with autoantibodies producing a cytoplasmic pattern and patients with autoantibodies producing a perinuclear pattern; however, the perinuclear pattern occurred more frequently in patients with renal-limited disease. Renal and patient survival was 75% at 24 months, and no difference in survival was seen between patients with renal-limited disease and those with systemic disease. No differences in survival were seen between patients treated with oral cyclophosphamide and those treated with intravenous cyclophosphamide; however, the comparative data from patients treated with corticosteroids alone were inconclusive. In general, autoantibody titers correlated with response to treatment and disease activity, but there were exceptions. CONCLUSIONS: Patients with ANCA have various forms of necrotizing vascular inflammation, ranging from renal-limited disease to widespread systemic vasculitis, including polyarteritis nodosa and Wegener granulomatosis. Oral corticosteroids with either oral or intravenous cyclophosphamide appear to be equally effective therapy for ANCA-associated glomerulonephritis.

Adolescent↗
PubMed1990

Diagnosis and management of glomerulonephritis and vasculitis presenting as acute renal failure.

Acute and rapidly progressive renal failure is caused by a number of pathogenetically distinct types of glomerulonephritis, some of which are associated with systemic vasculitis. In a given patient, accurate diagnosis of the specific type of glomerulonephritis is essential for optimum treatment. Making a specific diagnosis usually requires renal biopsy or serologic analysis. The two categories of treatment for glomerulonephritis are (1) treatment for the pathophysiologic complications of glomerulonephritis, such as hypertension, fluid overload, and uremia, and (2) treatment for the inflammatory injury, which usually employs immunosuppression with steroids and cytotoxic drugs.

Acute Disease↗
PubMed1990

Adult minimal change glomerulopathy with acute renal failure.

Oliguric acute renal failure occurs in some adult patients with minimal change glomerulopathy. To look for clinical and pathologic factors that increase the risk for developing acute renal failure, 21 adults with minimal change glomerulopathy and a serum creatinine greater than 177 mumol/L (mean, 486 mumol/L; range, 194 to 1,344 mumol/L) (greater than 2.0 mg/dL [mean, 5.5 mg/dL; range, 2.2 to 15.2 mg/dL]) were compared with 50 adults with minimal change glomerulopathy and a serum creatinine less than 133 mumol/L (mean, 88 mumol/L; range, 53 to 124 mumol/L) (less than 1.5 mg/dL [mean, 1.0 mg/dL; range, 0.6 to 1.4 mg/dL]). Minimal change glomerulopathy patients with acute renal failure were older (59.5 v 40.3 years, P less than 0.001), and had higher systolic blood pressure (158 v 138 mm Hg, P = 0.001), more proteinuria (13.5 v 7.9 g/24 h, P = 0.01), and more arteriosclerosis in the renal biopsy specimen (1.7 + v 0.7 + on a scale of 0 to 4+, P = 0.005). Tubular epithelial simplification identical to that observed with ischemic acute renal failure (acute tubular necrosis) was observed in 71% of the patients with serum creatinine greater than 177 mumol/L (greater than 2.0 mg/dL) and 0% of those with less than 133 mumol/L (less than 1.5 mg/dL). All 18 patients with renal failure for whom follow-up data were available had recovery of function (mean creatinine, 539 +/- 301 mumol/L [6.1 +/- 3.4 mg/dL] at the time of biopsy and 106 +/- 27 mumol/L [1.2 +/- 0.3 mg/dL] at last follow-up), but sometimes only after weeks of dialysis support.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

Antineutrophil cytoplasmic autoantibodies and associated diseases: a review.

Antineutrophil cytoplasmic autoantibodies (ANCA) are specific for constituents of neutrophil primary granules and monocyte lysosomes. There are different types of ANCA with different specificities. By indirect immunofluorescence microscopy using alcohol-fixed neutrophils as substrate, two major categories of ANCA can be recognized, one with cytoplasmic staining (C-ANCA) and the other with artifactual perinuclear staining (P-ANCA). Some C-ANCA have specificity for proteinase 3 (PR3-ANCA) and some P-ANCA have specificity for myeloperoxidase (MPO-ANCA), but there are additional C-ANCA and P-ANCA specificities. ANCA are found in the blood of patients with necrotizing systemic vasculitis, such as Wegener's granulomatosis and polyarteritis nodosa, and patients with idiopathic crescentic glomerulonephritis. The glomerular lesion in patients with systemic and renal-limited ANCA-associated diseases is the same, ie, a pauci-immune necrotizing and crescentic glomerulonephritis. No matter where the vascular lesions of ANCA-associated disease are (eg, kidney, lung, gut, muscle, skin), they are characterized by necrotizing inflammation and a paucity of immune deposits. The distribution of disease correlates to a degree with the ANCA specificity, although there is substantial overlap. For example, patients with Wegener's granulomatosis most often have C-ANCA and patients with renal-limited disease most often have P-ANCA. In patients with P-ANCA-associated glomerulonephritis, approximately 90% of the P-ANCA have specificity for MPO. The clinical manifestations of ANCA-associated diseases often begin following a flu-like illness. The onset is most often in the winter and least often in the summer. The renal disease usually presents as rapidly progressive renal failure with nephritis. One of the most life-threatening components of the systemic involvement is pulmonary hemorrhage caused by a necrotizing alveolar capillaritis. Intravenous cyclophosphamide plus steroids is as effective as oral cyclophosphamide plus steroids for controlling ANCA-associated diseases. Using life-table analysis, the 2-year patient and renal survival rate in both patients with renal-limited and systemic disease is greater than 70%. There is evidence that in addition to being a useful serologic marker, ANCA are directly involved in the pathogenesis of the vascular injury in patients with ANCA-associated diseases. Although ANCA antigens are normally in the cytoplasm of neutrophils and monocytes, priming of these cells, as occurs following exposure to certain cytokines, results in the release of small amounts of ANCA antigens at the cell surface. In vitro, ANCA-IgG causes cytokine-primed neutrophils to undergo a respiratory burst and degranulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed1990

Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are in the circulation of most patients with pauci-immune necrotizing vasculitis and pauci-immune crescentic glomerulonephritis. The current study demonstrates an effect of these autoantibodies on neutrophil function in vitro. ANCA cause normal human neutrophils to undergo an oxidative burst and degranulate. Both ANCA phenotypes (i.e., cytoplasmic-pattern ANCA and myeloperoxidase-specific ANCA) induce neutrophil activation. ANCA sera and purified immunoglobulins significantly increase the release of reactive oxygen species when compared with controls. ANCA, in a dose-dependent manner, induce the release of primary granule contents. These effects are markedly enhanced by priming neutrophils with tumor necrosis factor. Flow cytometry studies demonstrate the presence of myeloperoxidase on the surface of neutrophils after cytokine priming, indicating that primed neutrophils have ANCA antigens at their surfaces to interact with ANCA. These observations suggest an in vivo pathogenetic role for ANCA. We propose that, in patients with necrotizing vasculitis, ANCA-induced release of toxic oxygen radicals and noxious granule enzymes from cytokine-primed neutrophils could be mediating vascular inflammation.

Autoantibodies↗
PubMed1989

Microradiographic demonstration of human intrarenal microlymphatic pathways.

Renal lymphatics play a prominent role in physiological and pathologic states. However, intrarenal microlymphatic morphology has not been well established in humans. We have developed microangiographic techniques for studying microlymphatic morphology. Lymphatics were identified by location, presence of valves, and histologic characteristics in 4 patients (3 presented here and 1 reported previously), all of whom had congestive cardiac states. The renal lymphatics begin in the cortical interstitium near glomeruli and run adjacent to afferent arterioles and interlobular arteries. They drain into arcuate and interlobar vessels and then into hilar lymphatics. They also originate in and drain the medullary structures in the area of the vasa recta. Our study details the microlymphatic morphology in humans and confirms the similarity of human lymphatics to those studied extensively in pigs and dogs.

Adult↗
PubMed1989

Reactivity of anti-neutrophil cytoplasmic autoantibodies with HL-60 cells.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with antigens in the cytoplasm of neutrophils and monocytes, and are found in the blood of patients with necrotizing vasculitis and pauci-immune necrotizing and crescentic glomerulonephritis. The standard techniques for ANCA analysis use human polymorphonuclear leukocytes (PMN) as a source for antigen. A comparison was made between ANCA reactivity with human PMN and HL-60 cells. Fifty-five ANCA-positive and 17 ANCA-negative sera were reacted with HL-60 cells in an indirect immunofluorescence microscopy assay to assess the ability of HL-60 cells to distinguish between positive and negative reactivity and between the two major types of ANCA. The HL-60 cell method agreed with a PMN method in all but one instance. In an enzyme immunoassay, HL-60 primary granules could be used to detect ANCA. Evidence is also presented that the perinuclear staining of HL-60 cells and neutrophils by ANCA with anti-myeloperoxidase specificity is caused by the nucleophilic properties of myeloperoxidase. Reactivity with HL-60 cells further elucidates the antigen specificity of both types of ANCA and indicates that HL-60 cells are a suitable tissue culture cell line for investigating the pathobiology of ANCA.

Autoantibodies↗
PubMed1989

Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patients with renal disease, with and without systemic vasculitis, were analyzed. Of 76 patients with pauci-immune glomerulonephritis with crescents or necrosis, 87% had ANCA by IIFM (38% of C-ANCA type, 49% of P-ANCA type), and 78% had ANCA by EIA. Of 55 patients with nonlupus immune complex-mediated glomerulonephritis, only 11% had ANCA by IIFM and 5% had ANCA by EIA. Of 24 patients with anti-GBM antibody-mediated glomerulonephritis, none had ANCA. Renal and extrarenal lesions were studied in 81 patients with ANCA-associated glomerulonephritis. These patients formed a pathologic continuum ranging from renal-limited to widespread systemic vascular injury, including patients with primary crescentic glomerulonephritis, Wegener's granulomatosis, and polyarteritis nodosa. In ANCA-positive patients the frequency of C-ANCA and P-ANCA correlated with disease distribution. P-ANCA was most frequent with renal-limited disease and C-ANCA was most frequent when there was lung and sinus involvement. It is proposed that ANCA are not only useful diagnostic markers, but may also be directly involved in a novel pathogenetic mechanism that is a frequent cause of crescentic glomerulonephritis and systemic necrotizing vasculitis.

Adolescent↗
PubMed1988

Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis.

Anti-neutrophil cytoplasmic autoantibodies have been found in patients with systemic arteritis and glomerulonephritis. We studied the disease distribution and antigen specificity of these autoantibodies. Anti-neutrophil cytoplasmic autoantibodies were identified by indirect immunofluorescence microscopy in 27 of 35 patients with idiopathic necrotizing and crescentic glomerulonephritis, in whom the manifestations of disease ranged from injury limited to the kidney to systemic arteritis. The incidence and titers of the autoantibodies did not differ between patients with disease limited to the kidney and those with systemic disease. Anti-neutrophil immunostaining was detected in 5 of 11 patients with lupus nephritis, 4 of 71 patients with other renal diseases, and none of 50 normal controls. This distribution of autoantibodies was confirmed by an enzyme-linked immunosorbent assay (ELISA) using neutrophil lysate as antigen. According to ELISA, anti-neutrophil cytoplasmic autoantibodies were found to be specific for constituents of primary granules. Two types of autoantibodies were identified; one with reactivity with myeloperoxidase on ELISA produced an artifactual perinuclear immunostaining of alcohol-fixed neutrophils, and another with no reactivity with myeloperoxidase on ELISA produced diffuse cytoplasmic immunostaining. The presence of the same serologic marker in patients with kidney-limited and arteritis-associated necrotizing and crescentic glomerulonephritis, including Wegener's granulomatosis and polyarteritis nodosa, suggests that these clinically diverse diseases may have a similar pathogenesis, initiated by autoantibody-mediated activation of neutrophils.

Arteritis↗
PubMed1988

The immunohistology of IgA nephropathy.

The glomerular immunohistologic characteristics of 180 patients with IgA nephropathy (IgAN), defined by 2+ or greater (out of 0 to 4+) mesangial IgA-dominant or codominant immunostaining and no evidence for systemic lupus erythematosus, were compared with those of 84 patients with proliferative lupus glomerulonephritis and 254 patients with other forms of proliferative glomerulonephritis. The IgAN population increased in number by only 5% if the IgA immunostaining criterion was lowered to 1+, and it decreased by only 2% if IgA codominant staining was disallowed. A distinctive immunohistologic feature of IgAN in comparison with other immune complex-mediated glomerulopathies, in addition to the predominance of IgA immunostaining, was a high frequency (67%) of patients with greater lambda- than kappa-immunoglobulin light chain immunostaining. There was no correlation between the absolute or relative intensities or frequencies of IgA, IgG, or IgM immunostaining and the severity of glomerular disease; however, the presence of capillary wall immune deposits correlated with more severe disease. Terminal complement components were consistently present and were more conspicuous in more severely injured glomeruli. Immunostaining for the early classical complement activation pathway component C1q was absent or scanty in IgAN. This finding was particularly useful in the immunohistologic differentiation of IgAN from proliferative lupus glomerulonephritis, which was the form of glomerulonephritis with the greatest overlap with IgAN with respect to IgA immunostaining. When the diagnostic criteria for IgAN were 2+ or greater, dominant or codominant mesangial IgA immunostaining and less than 2+ C1q immunostaining, an immunohistologic diagnosis of IgAN was made with 98% accuracy.

Biopsy↗