Showing papers by "Philippe Lesavre published in 1991"

Light-Chain Composition of Serum IgA1 and In Vitro IgA1 Production in IgA Nephropathy

Abstract: A predominant expression of IgA1 in mesangial deposits, serum, and bone marrow culture supernatants has been shown in IgA nephropathy (IgAN). Furthermore an excess of lambda light chains in both mesangial deposits and serum IgA has been observed. However, the origin of mesangial IgA remains controversial. In the present study, we have examined the IgA1 light chain type in IgAN. Total IgA1, IgA1 kappa and IgA1 lambda were measured by ELISA in serum and culture supernatants from spontaneous and pokeweed-mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC). We observed an increase in IgA and IgA1 serum concentrations in IgA nephropathy patients, with a ratio of serum IgA1 to total serum IgA identical between patients and controls. The concentration of serum IgA kappa did not differ between patients and controls but patients had a significantly higher concentration of serum IgA lambda. The IgA1 kappa to IgA1 lambda ratio was 1.06 +/- 0.42 in IgAN patients versus 1.55 +/- 0.36 in controls (P less than 0.01). By contrast, the concentrations of IgA1 kappa and IgA1 lambda in PBMC culture supernatants, both spontaneous and PWM-stimulated, were identical in patients and controls. Therefore, there is a specific increase in IgA1 lambda in patients' sera. This contrasts with the normal IgA1 production by PBMC, which are derived from mucosal-associated lymphoid tissues. This suggests that IgA isotypic deregulation is confined to the bone marrow compartment and is not a generalised defect of the IgA system.

Antigen specificities and clinical distribution of ANCA in kidney diseases.

Abstract: The antigenic specificity and clinical distribution of the antineutrophil cytoplasmic antibodies (ANCA) in kidney diseases have recently been extensively studied. In patients with systemic vasculitis, the great predominance of two major ANCA antigens, proteinase 3 (PR3) and myeloperoxidase (MPO), is now established. PR3 and MPO are colocalized in the azurophilic granules of neutrophils and translocated to the cell surface during activation, and thus are able to interact with autoantibodies after neutrophil preactivation. Furthermore, by comparison of amino acid and DNA sequences, it has been shown that PR3 is identical to myeloblastin, which has been described independently and is involved in the control of growth and differentiation of leukemic cells. Aside from the two major ANCA antigens, a number of neutrophil cytoplasmic antigens recognized by ANCA have been identified, including human leukocyte elastase, lactoferrin, CAP57, and cathepsin G. These rare ANCA specificities occur in a limited number of patients. The variety of ANCA antigen specificities contrasts, however, with the fact that the vast majority of ANCA-positive sera are monospecific for one single ANCA antigen. With regard to clinical distribution, ANCA have major diagnostic significance in the four conditions in which they are frequently detected: Wegener's granulomatosis (WG), Churg and Strauss Syndrome (CSS), microscopic periarteritis (MPA), and necrotic and crescentic glomerulonephritis (NCGN). However, the initial dichotomy between MPO-associated vasculitis (NCGN, MPA) and that associated with anti-PR3 antibodies (WG) appears far from absolute.