Antineutrophil-cytoplasmic antibodies and antiglomerular basement membrane antibodies in Goodpasture's syndrome and in Wegener's granulomatosis

Abstract

Antiglomerular basement membrane (anti-GBM) diseases-including Goodpasture's (GP) syndrome-and Wegener's granulomatosis (WG) are systemic diseases, which may be diagnosed by means of circulating autoantibodies. Possible overlap syndromes may exist; however, they remain imperfectly defined. We analyzed sera from 31 patients with WG and from 23 patients with anti-GBM disease. All underwent biopsy. Anticytoplasmic antibodies (ANCA) were demonstrated by indirect immunofluorescence (HF); a perinuclear (P-ANCA) or diffuse-cytoplasmic (C-ANCA) staining was discerned. In addition, myeloperoxidase (MPO) antibodies (P-ANCA) and protein 3 (SP3) antibodies (C-ANCA) were analyzed by specific ELISA systems. Anti-GBM antibodies (anti-NC1 antibodies) were detected by ELISA and immunoblotting; the globular domain NC1 of collagen IV was employed as antigen. All 31 WG patients, as defined by clinical and histological criteria, showed ANCA by HF. Twenty-nine of 31 showed a C-ANCA pattern; all were also positive for SP3 antibodies by ELISA. Three of 31 WG patients were P-ANCA positive by IIF and also had anti-MPO antibodies by ELISA. In one of these patients, SP3 antibodies were additionally found by HF and by ELISA (double positive). No patient with WG had anti-NC1 antibodies. All 23 serum samples from patients with GP syndrome (N= 19) or anti-GBM glomerulonephritis (N = 4) had anti-NC1 antibodies. In seven of these patients, low titers of anti-MPO antibodies were detected by ELISA; however, the IIF for ANCA was negative. None of these seven patients had extraglomerular vasculitis. In addition, the clinical prognosis of these patients was similar to that of those patients who lacked these antibodies. One anti-NC1 positive-GP patient was also positive for SP3 antibodies (ELISA and IIP). On renal biopsy, an extraglomerular vasculitis was found in addition to the anti-GBM disease. We conclude that: (1) anti-NC1 antibodies are specific for GP syndrome or anti-GBM glomerulonephritis, (2) C-ANCA, i.e., SP3 antibodies may indicate WG, (3) low titers of MPO-antibodies occur in about one third of GP patients, and (4) anti-NC1 antibodies and SP3 antibodies (C-ANCA) may rarely occur concomitantly in GP patients with accompanying extraglomerular vasculitis.