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Antigen specificities and clinical distribution of ANCA in kidney diseases

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Summary

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.

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Abbreviations

ANCA:

antineutrophil cytoplasm antibodies

PR3:

proteinase 3

MPO:

myeloperoxidase

CAP57:

cationic antimicrobial protein 57 kDa

WG:

Wegener's granulomatosis

CSS:

Churg and Strauss syndrome

MPA:

microscopic periarteritis

NCGN:

necrotic and crescentic glomerulonephritis

IIF:

indirect immunofluorescence

HLE:

human leukocyte elastase

GBM:

glomerular basement membrane

IgAN:

IgA nephropathy

HSP:

Henoch-Schönlein purpura

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Authors and Affiliations

  1. Department of Nephrology and INSERM U90, Hôpital Necker, Paris

    P. Lesavre, L. H. Noël, D. Chauveau, C. Geffriaud & J. P. Grünfeld

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  1. P. Lesavre
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  2. L. H. Noël
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  3. D. Chauveau
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  4. C. Geffriaud
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  5. J. P. Grünfeld
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Additional information

Preprint of a lecture to be read at the 22nd Congress of the “Gesellschaft für Nephrologie”, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)

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Lesavre, P., Noël, L.H., Chauveau, D. et al. Antigen specificities and clinical distribution of ANCA in kidney diseases. Klin Wochenschr 69, 552–557 (1991). https://doi.org/10.1007/BF01649317

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