Role of antineutrophil cytoplasmic antibodies and glomerular basement membrane antibodies in the diagnosis and monitoring of systemic vasculitides

Abstract

This article was prepared at the invitation of the Clinical Sciences Reviews Committee of the Association for Clinical Biochemistry Systemic vasculitis, although rare, is often diagnosed late and long after the onset of symptoms. The small vessel vasculitides are recognized clinically by their multisystem presentation, markers of inflammation and evidence for an acute glomerulonephritis (GN), with the most apparent organ involved directing referral to secondary care. Routine laboratory tests are usually non-specific in systemic vasculitis but the use of anti-neutrophil cytoplasmic antibodies (ANCAs) and glomerular basement membrane (GBM) antibodies can aid diagnosis, treatment and monitoring decisions. These antibodies are detected and quantified by indirect immunofluorescence (IIF) and antigen-specific enzyme-linked immunosorbent assay (ELISA), usually in combination for ANCA, and ELISA systems (or direct IIF on kidney biopsy) for GBM antibodies. The presence or absence of ANCA does not confirm or exclude the diagnosis of systemic vasculitis but negative and positive predictive values will be strongly influenced by clinical presentation. Various large studies have been unable to conclude that following serial ANCA titres has great clinical utility in each case but each patient must be considered on its own merits; for example the reappearance of ANCA in a patient who was rendered ANCA negative following treatment is more likely to indicate relapse. The adoption of consensus guidelines that direct testing towards patients with rapidly progressive GN, pulmonary haemorrhage, persistent and destructive ear, nose and upper airways problems, such as subglottic tracheal stenosis, a retro-orbital mass and cutaneous vasculitis with systemic features or peripheral neuropathy, will greatly increase the clinical utility and positive predictive value of these tests.

Novel Clinical and Diagnostic Aspects of Antineutrophil Cytoplasmic Antibodies

“…Although controversially discussed, ANCA testing at intervals is recommended as ANCA titres may decline during effective treatment and often rise prior to relapse [21, 74, 75]. In contrast to IIF, tests that give quantitative ANCA measurements are required to monitor disease activity.…”

Anti-hLAMP2-antibodies and dual positivity for anti-GBM and MPO-ANCA in a patient with relapsing pulmonary-renal syndrome

“…This case highlights the importance of testing for coexistence of different antibodies in patients with PRS, as it may be a common manifestation of both SVV and Goodpasture's disease [5,6,17]. However, since the best long-term treatment of double-positive patients is unknown, an indicator for a relapsing SVV-like course of disease would be helpful.…”

Successful Treatment of Dual-Positive Anti-Myeloperoxidase and Anti-Glomerular Basement Membrane Antibody Vasculitis with Pulmonary-Renal Syndrome

“…In a survey of a series of 49 patients with PF associated with AAV, the eosinophil level was a poor prognostic factor, while initial pattern on thoracic high-resolution CT was not a prognostic factor [ 5 ]. The presence of positive MPO-ANCA was reported to be an unfavorable prognostic factor in patients with PF [ 6 ], and the detection of antibodies is necessary in monitoring disease relapse [ 7 ]. Our case adds knowledge to the former dual-positive cases with prior PF, in which the clinical presentation can also have a slower and better outcome.…”