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L H Noël

Publications and source records attributed to L H Noël.

At least 19 recordsLinked to original sources
PubMed2005

[Familial small-vessel vasculitis of the kidney].

INTRODUCTION: Familial forms of small-vessel vasculitis has been reported in 14 families (including this one). CASES: A father and son were both diagnosed with renal vasculitis (pauci-immune crescentic glomerulonephritis). Both had antimyeloperoxidase autoantibodies, and there was no evidence of a common environmental factor. DISCUSSION: These cases suggest the role of constitutional factors in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis.

Aged↗
PubMed2001

Granulomatous renal disease in a patient with common variable immunodeficiency.

Common variable immunodeficiency (CVID), the most common cause of primary hypogammaglobulinemia, is characterized by a decreased serum immunoglobulin level, recurrent infections, and the occurrence of various autoimmune diseases. Granulomatous disease has been reported previously in several patients with CVID, with granuloma occurring in the lymph nodes, spleen, liver, central nervous system, and bone marrow. We report the first published case of renal granulomatous disease in a CVID patient presenting with subacute renal failure. Renal function partially recovered after corticosteroid treatment and intravenous immunoglobulin infusions. The pathogenesis of granulomatous disease in CVID is unclear but may involve monocyte and T-cell abnormalities.

Adult↗
PubMed2001

Are antineutrophil cytoplasmic antibodies a marker predictive of relapse in Wegener's granulomatosis? A prospective study.

OBJECTIVES: To investigate the predictive value of testing for antineutrophil cytoplasmic antibodies (ANCA) in 55 patients with systemic Wegener's granulomatosis (WG) included in a randomized, prospective trial comparing corticosteroids and oral or pulse cyclophosphamide. METHODS: All 55 patients received corticosteroids. A cyclophosphamide pulse of 0.7 g/m2 was given at the time of diagnosis. After the first pulse, the patients were assigned at random to receive either pulse or oral cyclophosphamide (2 mg/kg/day), independently of ANCA results. ANCA were sought using an immunofluorescence assay and an attempt was made to correlate them with relapse of WG. ANCA were monitored throughout the study. RESULTS: At the time of diagnosis, ANCA were detected in 48 (87%) patients, with a cytoplasmic labelling pattern in 44 and a perinuclear pattern in four. ANCA follow-up was available for 50 patients. ANCA disappeared in 34 patients and persisted in nine. For 79% of the patients, the clinical course improved with the disappearance of ANCA and deteriorated with their persistence or increased titre. Among the patients who were initially ANCA-positive, 23 relapses occurred. Relapses were more frequent when ANCA remained positive or reappeared [13/19 ANCA-positive patients vs 3/29 ANCA-negative patients (P<0.01)]. Nine relapses (39%) occurred in patients with persistent ANCA, and ANCA reappearance preceded relapse in eight (35%). The mean time between inclusion and relapse did not differ between the patients who became ANCA-negative and those who were persistently ANCA-positive (14.6+/-13.2 vs 14.4+/-8.2 months). The mean time to ANCA disappearance was similar for the patients who relapsed and those who did not. Corticosteroids and pulse or oral cyclophosphamide did not significantly modify the time to ANCA disappearance. Throughout the study, seven patients were ANCA-negative. CONCLUSION: Although ANCA positivity was associated with relapse, discordance between cytoplasmic ANCA and disease activity was not unusual. In the absence of clinical manifestations, ANCA titres alone can serve as a warning signal but not indicate whether to adjust or initiate treatment.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

[Causes and mechanisms of vasculitides].

Vasculitic lesions are defined by necrosis of the vascular wall with perivascular inflammatory infiltrates. Secondary forms of vasculitis are observed in some systemic diseases, after infections, secondary to drugs or to malignancies. Usually, these secondary forms are characterised by the presence of immunoglobulin and complement deposits and thus probably caused by immune complex deposits. Conversely, necrotizing vasculitis occurring without known causal factor are named primary vasculitis, are not associated with immune deposits. Wegener's granulomatosis, microscopic polyangitis, Churg and Strauss syndrome and the isolated form of necrotizing and crescent glomerulonephritis are closely associated with the anti-neutrophil cytoplasm auto-antibodies (ANCA). The two main auto-antigen targets recognised by ANCA are lysosomal enzymes, proteinase 3 and myeloperoxidase, both contained in azurophilic granules of polymorphonuclear neutrophils and in primary lysosomes of monocytes. It has been demonstrated that ANCA antigens are expressed at the neutrophil (and monocyte) membrane after preactivation and are accessible to antibodies. Thus, ANCA may amplify neutrophils and monocyte activation. However, the causal or induced nature of anti-neutrophil auto-immunity in vasculitis remains unknown.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Cyclosporine withdrawal in stable renal transplant recipients after azathioprine-mycophenolate mofetil conversion.

BACKGROUND: Cyclosporine A (CsA) nephrotoxicity is a nonimmunologic factor of chronic allograft dysfunction (CAD) in kidney transplant recipients. Mycophenolate mofetil (MMF) may allow CsA dosage reduction or even complete withdrawal in selected populations with CsA nephrotoxicity or CAD. The aim of the present study was to evaluate the efficacy and safety of CsA withdrawal after azathioprine (AZA)-MMF conversion in a population of stable renal transplant recipients. METHODS: Twenty-eight first cadaver kidney recipients were included. AZA was then discontinued, MMF was introduced and after 4 months CsA was completely withdrawn. All patients underwent inuline clearance measurement and renal biopsy at inclusion and at the end of the follow-up (40 wk). RESULTS: CsA was completely discontinued in 20 patients. No patient lost his graft during the study period, but 1 patient experienced a reversible acute rejection episode. Inuline clearance improved significantly in the whole series. At the end of follow-up, histological worsening was observed in 50% of patients without any specific risk factor. In these patients, inuline clearance did not improve. Systolic blood pressure, the need for anti-hypertensive drugs and HDL cholesterol improved. CONCLUSION: In stable kidney transplant recipients, CsA withdrawal after AZA replacement by MMF switch was safe with regard to acute rejection. It improved blood pressure and the lipid profile, but, in 50% of patients was associated with histologic deterioration.

Adult↗
PubMed2000

Renal pathology and ultrastructural findings in Alport's syndrome.

Morphological study of the kidney is generally the first step in the diagnosis of Alport's syndrome. Light microscopy study allows to suggest the diagnosis with the association of focal and segmental glomerulosclerosis, GBM anomalies when studied with silver staining, interstitial foam cells, and negative standard immunofluorescence study. GBM anomalies observed by electron microscopy are nearly specific with thickening splitting and fragmenting of the lamina densa. GBM anomalies are the consequence of a collagen IV disease. Thus, immunohistochemical results obtained with 6 different alpha(IV) are essential and allow to evaluate the mode of inheritance. Schematically, in the X dominant AS form, GBM, distal tubular BM and collecting duct BM do not express alpha3/alpha4, alpha5(IV). In the autosomic recessive AS form, collecting duct BM alone express alpha5(IV) without expression of alpha3(IV) and alpha5(IV) chains along the GBM and distal TBM.

Basement Membrane↗
PubMed2000

Distribution of alphavbeta3, alphavbeta5 integrins and the integrin associated protein--IAP (CD47) in human glomerular diseases.

The alphav integrins present on the membrane of numerous cells, mediate attachment to matrix proteins, cell proliferation, migration and survival. We studied the expression of alphav integrinis and CD47 (a beta3 chain integrin associated protein) in various forms of glomerulonephritis (GN) characterized by mesangial proliferation and/or increased mesangial matrix. In normal glomeruli, epithelial cells expressed alphavbeta3, alphavbeta5 and CD47; endothelial cells expressed alpha5beta1 and CD47; mesangial cells expressed alphavbeta5, CD47, and to a less extent alphavbeta3. In acute post infectious GN (APIGN), membrano-proliferative GN (MPGN) and diabetic nephropathy(DN), we observed that the beta3 chain, normally expressed by mesangial cells, was not detectable in the mesangium while its expression by epithelial cells was not modified. Parallel to the disappearance of alphavbeta3, the CD47 expression was decreased on the mesangial cells in MPGN, APIGN and DN. The expression of alphavbeta5 was clearly increased on podocytes and on proliferating mesangial cells in APIGN. By contrast, the mesangial expression of alphavbeta was normal or decreased in DN. The alpha5 chain of integrin, absent on normal mesangial cell, was expressed on proliferating mesangial cells in MPGN and APIGN. Thus, we observed modifications of alphavbeta3 and alphavbeta5 expression during human GN. The modulations of alphavbeta3 and alphavbeta5 expression differed according to the different glomerular cell types and were not parallel in glomerular cells: alphavbeta3 was decreased (and alphavbeta5 unchanged) on proliferating mesangial cells and alphavbeta5 was increased (and alphavbeta3 unchanged) in podocytes. This may reflect the existence of two distinct regulatory pathways.

Antibodies, Monoclonal↗
PubMed2000

[Antineutrophil cytoplasm antibodies (ANCA): description and immunopathological role].

These antibodies are specific for antigens in the cytoplasm of neutrophils. The main antigenic targets are proteinase 3(PR3) and myeloperoxydase (MPO) but other targets have been described without determinant conclusions for clinical practice. Staining patterns can be distinguished by an indirect immunofluorescence test (IFI), in which ethanol fixed neutrophils from healthy donors are incubated with patient's sera. Two patterns are distinguished: cytoplasmic pattern (c-ANCA) and perinuclear pattern (p-ANCA). When ANCA are detected by IFI, from a practical point of view, anti -MPO and anti-PR3 antibodies are tested. ANCA have been strongly associated with a spectrum of necrotizing small vessel vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis, Churg and Strauss syndrome, pauci-immune focal necrotizing and crescentic glomerulonephritis. ANCA are a diagnosic marker and useful for the follow-up of the patients. ANCA can be observed in other pathologies: rhumatismal autoimmune diseases, inflammatory gut diseases, after drugs (hydralazine, minocycline, propylthiouracil), after silical exposition, infections (cystic fibrosis, endocarditis, HIV infection). The specificity is different and rarely anti-MPO. The ANCA role for the development of vasculitis is not completely elucidated. Some arguments are against a primary role of ANCA in the development of vasculitis. Certainly, amplification role for neutrophil activation is demonstrated but the primary event responsible of neutrophil activation is not yet defined.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis.

BACKGROUND: In kidney biopsies of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis, a variety of histopathological lesions occur, and their relationship to renal outcome is virtually unknown. This multicenter European study reports a clinicopathological analysis of biopsies from 157 patients with systemic vasculitis. METHODS: The biopsies were evaluated according to a previously standardized scoring protocol. Serum creatinine values were measured at the time of biopsy and one year later. In addition, the lowest creatinine level during follow-up was taken into account as the optimum level of renal function recovery. The clinical prognostic value of the histopathological parameters was analyzed with the Kruskal-Wallis one-way analysis of variance and the Mann-Whitney U-test. RESULTS: The percentage of normal glomeruli correlated most significantly with renal outcome at all points of measurement (all P < 0.001). Other lesions predicting for renal function were glomerular sclerosis (P < 0.0005 at one year after the biopsy), diffuse interstitial infiltrates (P < 0.0001 at entry, P < 0.0003 at one year), tubular necrosis (P < 0.0025 at entry), and tubular atrophy (P < 0.002 at entry, P < 0.0002 at one year). CONCLUSION: Traditionally, attention is focused on the extent of active lesions in the renal biopsy in order to determine the severity of renal disease and its implication for renal outcome. Because of their significant impact on renal function, combined with their easy recognition, we recommend the use of the percentage of normal glomeruli in an adequate biopsy in predicting renal function of patients with systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Morphological features of primary focal and segmental glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSGS) is one of the most common and non-specific patterns of glomerular injury encountered in human renal biopsies. The primary form can be considered when there is a nephrotic syndrome without other causes. The majority of authors agree that podocytes play a role in the development of segmental glomerulosclerosis. The lesion begins with cell hypertrophy, foot process effacement, cell body attenuation, pseudocyst formation, cytoplasmic overload with reabsorption droplets and finally detachment of the glomerular basement membrane (GBM). When the GBM is denuded, it comes into contact with the parietal epithelium and parietal epithelial cells will attach to the GBM, leading to a synechia and, finally, sclerosis. Along this zone, parietal epithelial cells rest on hyalin material. Occlusion and collapse of a group of capillaries is observed, with inclusion of foam cells and hyalin deposits. The origin of primary FSGS has not yet been elucidated. Genetic, racial and developmental factors, macrophages, viral factors and circulating factors are being explored and give encouraging results.

Basement Membrane↗
PubMed1999

A large subset of neutrophils expressing membrane proteinase 3 is a risk factor for vasculitis and rheumatoid arthritis.

It has been shown previously that proteinase 3 (PR3), a neutrophil intracellular protease that is the main antigen of antineutrophil cytoplasm (ANCA) autoantibodies, is present on the plasma membrane of a subset of freshly isolated neutrophils. This study shows that the size of this subset of membrane PR3-positive (mPR3+) neutrophils is a stable feature of a given individual, most likely genetically controlled. It ranges from 0 to 100% of neutrophils and allows us to define a new polymorphism in the healthy population, with three discrete phenotypes corresponding respectively to less than 20% mPR3 + neutrophils (mPR3low) or to a mean percentage of 47% (mPR3intermediate) and 71.5% (mPR3high) mPR3+ neutrophils. The frequency of the mPR3high phenotype was significantly increased in patients with ANCA-associated vasculitis (85% versus 55% in healthy subjects). The percentage of mPR3+ neutrophils was not affected by disease activity, relapses, or therapy, and did not reflect in vivo cell activation. In addition, mPR3+ phenotypes were normally distributed in cystic fibrosis patients, indicating that infection and/or inflammation per se do not lead to a high percentage of mPR3+ neutrophils. The frequency of the mPR3high phenotype was not related to anti-PR3 autoimmunization, since it was increased in vasculitic patients regardless of the ANCA specificity (anti-PR3, anti-myeloperoxidase, or unknown). Interestingly, the frequency of the mPR3high phenotype was also increased in patients with rheumatoid arthritis. It was normal in type I-diabetes, a T cell-dependent autoimmune disease. It is proposed here that a high proportion of membrane PR3-positive neutrophils could favor the occurrence or the progression of chronic inflammatory diseases.

Adult↗