Anti-Neutrophil Cytoplasmic Autoantibodies with Specificity for Myeloperoxidase in Patients with Systemic Vasculitis and Idiopathic Necrotizing and Crescentic Glomerulonephritis

TLDR

Let's gather content. Background: "Anti-neutrophil cytoplasmic autoantibodies have been found in patients with systemic arteritis and glomerulonephritis." Purpose: "We studied the disease distribution and antigen specificity of these autoantibodies." Mechanism: includes sentences labeled Mechanism or Mechanism, Findings. Let's collect all Mechanism content: - From line 3: "[Mechanism, Findings] 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." - From line 5: "[Mechanism, Findings] 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." - From line 6: "[Mechanism] This distribution of autoantibodies was confirmed by an enzyme-linked immunosorbent assay (ELISA) using neutrophil lysate as antigen." So Mechanism content: identification by indirect immunofluorescence microscopy in 27/35 patients with idiopathic necrotizing and crescentic glomerulonephritis; immunostaining detected in lupus nephritis, other renal diseases, none in controls; confirmed by ELISA using neutrophil lysate. Let's collect: - Line 3 (Mechanism, Findings): same as above: "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." - Line 4: "The incidence and titers of the autoantibodies did not differ between patients with disease limited to the kidney and those with systemic disease." - Line 5: "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." - Line 7: "According to ELISA, anti-neutrophil cytoplasmic autoantibodies were found to be specific for constituents of primary granules." - Line 8: "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." - Line 9: "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." So Findings summary: They found anti-neutrophil cytoplasmic autoantibodies in 27/35 patients with idiopathic necrotizing and crescentic glomerulonephritis, with similar incidence and titers in kidney-limited vs systemic disease; immunostaining also seen in lupus nephritis and other renal diseases but not controls; ELISA showed specificity for primary granule constituents; two autoantibody types identified, one MPO-reactive causing artifactual perinuclear staining, the other non-MPO reactive causing diffuse cytoplasmic staining; presence across diverse diseases suggests common pathogenesis via neutrophil activation. Must be concise but include key points.

Abstract

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. (N Engl J Med 1988; 318:1651–7.)