Wegener's granulomatosis and other inflammatory disorders

Antineutrophil cytoplasmic antibodies (ANCAs) constitute a new class of autoantibodies that seem to recognise myeloid lysosomal enzymes. The occurrence of ANCAs with specificity for human leucocyte elastase (HLE) was assessed in serum samples that were routinely submitted for ANCA determination. During a study period of more than six years anti-HLE was found in only six out of 1102 serum samples that produced a perinuclear or an atypical cytoplasmic staining pattern on ethanol fixed granulocytes. These six serum samples were from four patients with a clinical diagnosis of Wegener's granulomatosis but without a definite histological diagnosis, one patient with systemic vasculitis, and one patient with Cogan's syndrome. To further evaluate the prevalence of anti-HLE we tested 315 serum samples from patients with different forms of vasculitis and related disorders. Anti-HLE was detected in two patients only. Thus autoantibodies to HLE are rarely found in serum samples from patients with vasculitic or related disorders. (Ann Rheum Dis 1993; 52: 115-120) Department of Clinical Immunology, University Hospital, Groningen, The Netherlands J W Cohen Tervaert L Mulder C Stegeman M Huitema H The C Kallenberg Department of Pathology, University Hospital, Groningen, The Netherlands J Elema Correspondence to: Dr C G M Kallenberg, Department of Clinical Immunology, University Hospital, Oostersingel 59, 9713 EZ Groningen, The Netherlands. Accepted for publication 9 September 1992 The demonstration of autoantibodies to neutrophil cytoplasmic antigens (ANCAs) in systemic vasculitides such as Wegener's granulomatosis, classic polyarteritis nodosa, and the ChurgStrauss syndrome, and in idiopathic crescentic glomerulonephritis has placed these disorders within the class of autoimmune diseases.' Two major types of ANCAs have been recognised.2 The first type is called c-ANCA ('classic' or 'cytoplasmic' ANCA) and is strongly associated with Wegener's granulomatosis.'5 These antibodies produce a characteristic granular cytoplasmic staining pattern on ethanol fixed granulocytes when detected by a standard indirect immunofluorescence technique.6 Recently, it has been shown that the antigen recognised by c-ANCA is identical to proteinase 3, a 29 kilodalton glycoprotein from azurophilic granules with serine protease, antibiotic, and myeloblastic activity.7`1 The second type of ANCA is called p-ANCA ('perinuclear' ANCA). A substantial number of p-ANCA positive serum samples were shown to contain autoantibodies to myeloperoxidase.'2 13 These antibodies produce a perinuclear pattern on ethanol fixed cytocentrifuged granulocytes, but a cytoplasmic staining pattern when granulocytes are treated with cross linking fixatives,'2 or when freshly prepared thin blood smears are used as a substrate. 4 Myeloperoxidase antibodies are found in patients with idiopathic crescentic glomerulonephritis (that is, without systemic vasculitis), crescentic glomerulonephritis associated with vasculitis, or alveolar haemorrhage, or both, hydralazine induced glomerulonephritis, and in patients with ChurgStrauss syndrome or classic polyarteritis nodosa.'12 13 1517 Recently, it became apparent that a substantial number of p-ANCA positive serum samples do not react with myeloperoxidase.'6 18 19 Serum samples positive for p-ANCA but negative for myeloperoxidase antibodies may be directed to other myeloid enzymes, such as human leucocyte elastase (HLE)7 " or lactoferrin. 9 20 Antibodies to HLE have been described in some patients with vasculitis,'7 21 in patients with hydralazine induced glomerulonephritis,'5 and occasionally in patients with systemic lupus erythematosus.'5 22 Because the clinical significance, that is, the prevalence and possible clinical associations of autoantibodies specific for HLE is not well delineated, we further investigated the clinical associations of these antibodies by analysing clinical data of all consecutive patients whose serum samples were routinely submitted for determination of ANCAs and were positive for HLE antibodies. We also tested for the prevalence of this autoantibody in a large group of clinically well characterised patients. Patients and methods