Antineutrophil Cytoplasmic Antibody Antigens Research Articles

Lack of IgA Antineutrophil Cytoplasmic Antibodies in Henoch-Schönlein Purpura and IgA Nephropathy

To verify whether IgA antineutrophil cytoplasmic antibody (ANCA) represents a serologic marker in Henoch-Schönlein purpura (HPS), we examined sera from 41 patients with the disease. Control sera from 28 patients with primary IgA nephropathy (IgA-N), 26 IgG-ANCA-positive vasculitis, and 28 normal controls were also studied. An increased IgA binding to neutrophil cytoplasmic extracts but not to purified ANCA antigens was found in 12.2-14.6% of HSP patients and in 14.3-21.4% of IgA-N patients versus 3.5% of normal controls. IgA binding to neutrophil cytoplasmic extracts correlated with serum IgA levels, IgA-rheumatoid factor, and IgA-fibronectin binding capacity. Moreover, low amounts of IgG and fibronectin were detected as contaminants in neutrophil cytoplasmic extracts and fibronectin could partly inhibit the binding of IgA to "crude" extracts. We conclude that IgA-ANCA are neither diagnostically nor immunologically specific in HSP and IgA-N. Several factors present in the sera of patients with IgA-related nephropathies seem to contribute to the "false-positive" IgA-ANCA demonstrable in these patients.

Antigen specificities and clinical distribution of ANCA in kidney diseases

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.