Detection and clinical implication of anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis and rapidly progressive glomerulonephritis

The specificity of anti-neutrophil cytoplasm antibodies (ACPA/ANCA) was investigated in patients suffering from Wegener's granulomatosis (WG), various forms of systemic diseases including vasculitides (non-WG), and different types of biopsy-proven glomerulonephritides. In particular, the diagnostic significance of ACPA/ANCA was assessed in patients affected by rapidly progressive glomerulonephritis with and without systemic manifestations. From 25 patients with active Wegener's granulomatosis 22 showed the classical diffuse finely granular cytoplasmic staining of neutrophils as did 4/31 patients with idiopathic rapidly progressive glomerulonephritis. One patient with biopsy confirmed Wegener's granulomatosis, six patients with microscopic polyarteritis and 3/31 patients with idiopathic rapidly progressive glomerulonephritis showed a focal cytoplasmic staining exhibiting a rosette-like pattern. One further patient with Wegener's granulomatosis displayed a prominent fluorescence of the outer nuclear membrane as well as a punctate-diffuse nuclear staining resembling that of granulocyte specific antibodies. Another patient with active Wegener's granulomatosis did not react in the ACPA/ANCA-test. These findings demonstrate different staining patterns of neutrophils which are related to different clinical entities within the spectrum of small vessel vasculitis. Moreover, they point out that different antigens are involved in the various types of vasculitis. In classical cases of Wegener's granulomatosis, but not in other forms of vasculitis, the titer of ACPA/ANCA showed a close relationship to the number of organs involved.     

Clinical relevance of testing for antineutrophil cytoplasm antibodies (ANCA) with a standard indirect immunofluorescence ANCA test in patients with upper or lower respiratory tract symptoms.

BACKGROUND--Reports from specialist nephrological centres have suggested that the antineutrophil cytoplasm antibody (ANCA) test is highly specific and sensitive for patients with Wegener's granulomatosis. To determine the usefulness of the ANCA test in everyday respiratory practice the results of the test were audited in all patients in the south west of England with respiratory symptoms who underwent the test. METHODS--The results of all 335 patients who had presented with upper or lower respiratory tracts symptoms, or both, and were tested for ANCA by the indirect ANCA test in 1990, as recommended in the broadsheet of the British Association of Clinical Pathologists, were audited. Case notes and necropsy reports were available for review in 231 cases (69%), and in the remainder information was obtained by a standard questionnaire. RESULTS--There were 106 positive results, 45 (44%) from patients with Wegener's granulomatosis. The sensitivity and specificity of a positive ANCA test result in this study were 65% and 77% respectively. For a diagnosis of Wegener's granulomatosis the sensitivity and positive predictive accuracy of a positive cytoplasmic ANCA (c-ANCA) test were greater than of a positive perinuclear ANCA (p-ANCA) test. There were 61 positive tests in 266 patients who did not have Wegener's granulomatosis (23%); of these 27 were from patients with infection, 10 with fibrotic lung disease, nine with underlying connective tissue disease, seven with malignancy, and five following pulmonary emboli. Most of these positive ANCA results were p-ANCA (69%) rather than c-ANCA (31%). Serial ANCA requests were made in 15 cases of patients without Wegener's granulomatosis who had an initial positive ANCA test result. In all cases the ANCA tests subsequently became negative. CONCLUSIONS--In this study the sensitivity and specificity of a positive ANCA test result were less than that reported from specialised centres. However, the test was found to be useful in clinical practice, especially c-ANCA, in conjunction with clinical symptoms of respiratory pathology and evidence of renal disease.     

HLA class II specificities in vasculitis with antibodies to neutrophil cytoplasmic antigens.

HLA class II genes were examined in patients with small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA) using restriction fragment length polymorphism and allele specific oligonucleotide typing. Fifty-nine patients were studied, 34 with Wegener's granulomatosis and 25 with microscopic polyarteritis, and their results were compared with those from 1103 British Caucasoid controls. The frequency of HLA-DQw7 was significantly increased in patients with vasculitis (patients 53%; controls 27.8%, chi 2 17.8, Pc less than 0.0025, relative risk 2.9), and all the DQw7 bearing haplotypes commonly found in Caucasoid populations contributed to the increase. By contrast, the frequency of HLA-DR3 bearing haplotypes was decreased in the patients (patients 6.8%; controls 21.6%, chi 2 6.7, P less than 0.01). HLA specificities were similar in the groups of patients presenting with Wegener's granulomatosis and microscopic polyarteritis and with different types of ANCA assessed by indirect immunofluorescence. However, patients with the DQw7, DR4 haplotype were significantly more likely to have transiently positive tests for ANCA than patients with other DQw7 bearing haplotypes, whereas patients with DR2 bearing haplotypes were more likely to have persistently positive ANCA. These results show that HLA class II genes are associated with small vessel vasculitis and may influence the duration of the associated autoimmune response.     

Clinical investigation of anti-myeloperoxidase antibodies in patients with glomerulonephritis with crescent formation

Anti-neutrophil cytoplasmic antibodies (ANCA) have been found in patients with systemic vasculitis and crescentic glomerulonephritis. Recently two types of ANCA were identified, one is anti-myeloperoxidase antibodies (Anti-MPO Ab) stained perinuclear pattern of alcohol-fixed neutrophils by immunofluorescence test, and the other is autoantibodies with no reactivity with myeloperoxidase stained diffuse cytoplasmic pattern (C-ANCA). We investigated 59 patients with various glomerulonephritis with or without crescent to detect anti-MPO Ab and C-ANCA by an enzyme-linked immunosorbent assay. The results were as follows: 1) Anti-MPO Ab were detected only in patients with various glomerulonephritis with crescent. 2) Titers of anti-MPO Ab were high related to percentage of crescent in some cases of glomerulonephritis. 3) Titers of anti-MPO Ab were elevated at stage of cellular and fibro-cellular crescent. 4) C-ANCA were detected only in patients with Wegener's granulomatosis. These data suggested that anti-MPO Ab may play important roles in crescent formation and may be a marker of crescent formation in various glomerulonephritis.     

Antimyeloperoxidase antibodies in patients with extracapillary glomerulonephritis

The sera of 64 patients with extracapillary glomerulonephritis were investigated by enzyme-linked immunosorbent assay for the presence of antibody to human neutrophil myeloperoxidase (MPO). In all, circulating anti-MPO were found in 30% and antineutrophil cytoplasm antibodies (ANCA) detected by indirect immunofluorescence in 44% of the patients. Autoantibody to components of neutrophil granulocytes was not found in patients with other forms of glomerulonephritis. The incidence of ANCA (16/23) was higher than that of anti-MPO (5/23) in patients with a diagnosis of Wegener's granulomatosis. By contrast, anti-MPO was found in a majority of vasculitis patients without extrarenal symptoms (6/9), including 3 patients treated with hydralazine. One of the patients treated with hydralazine had circulating ANCA in combination with anti-MPO. Anti-MPO was also found in 1 out of 6 patients with Goodpasture's syndrome. The findings emphasize that autoantibodies to distinct components of neutrophil granulocytes partly differ with regard to diagnostic specificity.     

Diagnostic classification of antineutrophil cytoplasmic autoantibody-associated vasculitides

Antineutrophil cytoplasmic autoantibodies (ANCA) are in the circulation of patients with a variety of clinically and pathologically distinctive forms of necrotizing vasculitis. Some patients have classic manifestations of well-recognized clinicopathologic syndromes, such as Wegener's granulomatosis, microscopic polyarteritis nodosa, and Churg-Strauss syndrome, but many patients are difficult to assign to a diagnostic category. The Ad Hoc Nomenclature Committee of The Third International Workshop on ANCA is attempting to identify a working classification system for ANCA-associated vasculitides. This system takes into account the many shared clinical and pathologic features, and relies on prerequisite positive and negative findings for diagnostic categorization.     

Antineutrophil cytoplasmic autoantibody-associated diseases: a rheumatologist's perspective

Autoantibodies against neutrophil cytoplasmic antigens (ANCA) produce two major immunofluorescence (IF) patterns on ethanol-fixed granulocytes: the "classical" (centrally accentuated) C-ANCA, associated with Wegener's granulomatosis (WG), and P-ANCA (perinuclear), which mainly occur in renal vasculitis. Rheumatic manifestations are an important clinical finding in systemic vasculitis, often preceding a fulminant course and sometimes imitating various rheumatic disorders. We analyzed the incidence of ANCA in rheumatic patients and looked for the frequency of rheumatic symptoms in systemic vasculitis. In WG (n = 186), we found rheumatic symptoms in 55% (myalgia, 45%; arthritis, 21%); in 90%, rheumatic complaints were associated with active vasculitis. In 730 patients with various rheumatic conditions (eg, 268 rheumatoid arthritis, 130 systemic lupus erythematosis [SLE], 32 sharp-S, 50 ankylosing spondylitis, 43 systemic sclerosis) no C-ANCA were found. On the contrary, the P-ANCA pattern was seen in seven of 62 giant cell arteritis, five of 27 Felty's/Still's syndrome, and four of 130 SLE patients in addition to renal vasculitis (21/74). We demonstrated that 95% of C-ANCA-positive sera react with proteinase 3 (PR3 or myeloblastin). Using monoclonal antibodies, we showed that PR3 is expressed on the plasma membrane of neutrophil granulocytes and monocytes; thus, PR3 autoantigens are accessible for circulating antibodies. The detection of ANCA in sera from vasculitis and other rheumatic diseases is of immunodiagnostic value and provides new insight in the pathogenesis of systemic vasculitides.     

Anti-myeloperoxidase autoantibodies in patients with necrotizing glomerular and alveolar capillaritis.

We conducted a prospective study of 651 Mediterranean patients from Catalonia (Spain) with well-defined forms of systemic vasculitis, connective tissue diseases, and renal and pulmonary disorders to determine the prevalence and clinical value of antineutrophil cytoplasmic autoantibodies (ANCA) with myeloperoxidase (MPO) specificity (MPO-ANCA). ANCA were first tested by indirect immunofluorescence on ethanol-fixed neutrophils. When a positive result was obtained, then MPO-ANCA were identified by performing the immunofluorescence assay again on neutrophils from a voluntary donor known to have a complete and selective deficiency of MPO. This disorder was detected by automated flow cytochemistry with the Technicon system and was further verified by cytochemical and biochemical studies. We detected MPO-ANCA in 61 of 70 (87%) patients with a perinuclear pattern (p-ANCA), but in none of 25 with a cytoplasmic pattern (c-ANCA). These results were corroborated by enzyme-linked immunosorbent assay (ELISA) using human purified MPO as a substrate. On immunofluorescence microscopy, all patients with MPO-ANCA were found to have a typical and restrictive immunostaining pattern. In our study, while c-ANCA were mainly found in patients with biopsy-proven Wegener's granulomatosis, MPO-ANCA identified those with idiopathic and polyarteritis nodosa-associated necrotizing and crescentic glomerulonephritis. In addition, pulmonary hemorrhage with necrotizing alveolar capillaritis as the main morphologic substrate occurred frequently among patients with MPO-ANCA, including three affected by polyarteritis nodosa and three who had pulmonary hemorrhage as the only clinical finding. On the other hand, these antibodies could be also detected in 30% of patients with a proven diagnosis of anti-glomerular basement membrane (GBM) disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-neutrophil cytoplasmic antibody-associated vasculitis, large vessel vasculitis and Kawasaki disease in Japan

Based on studies comparing the prevalence of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) between Japan and Europe, we have learned that the difference may be due to genetic background and environmental factors, but not to diagnosis or ELISA system for myeloperoxidase and proteinase-3 ANCA. In Japan, microscopic polyangiitis is the most common among AAV, but Wegener's granulomatosis was present in less than 2 per million patients. Also, one study from Hokkaido reported only 16 patients in a 27-year time frame. A recent retrospective study of renal vasculitis between 2000 and 2004 from Miyazaki prefecture in Japan reported an incidence of microscopic polyangiitis of 14.8 per million, but no patients with Wegener's granulomatosis or Churg-Strauss syndrome. In the present review, we focus on ANCA-related vasculitis in Japan: (1) AAV and large vessel vasculitis - Takayasu's arteritis and giant cell arteritis; (2) primary renal vasculitis; (3) epitopes of myeloperoxidase-ANCA in vasculitis in the Japanese population and comparison of ANCA-ELISA systems in Japan and Europe, and finally (4) children with vasculitis in Japan involving Kawasaki disease - a systemic vasculitis.     

Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in collagen diseases associated with vasculitic syndrome in Japan.

The present study was undertaken to determine the anti-neutrophil cytoplasmic antibody (ANCA) levels in 96 patients with various collagen diseases associated with renal vasculitis and vasculitic syndrome in Japan. The results indicated that cytoplasmic(C)-ANCA is an autoantibody highly specific to Wegener's granulomatosis (WG) and that it is also active in renal injury. The relationships between ANCA and focal segmental necrotizing GN, i.e., renal vasculitis as proposed by Balow, were investigated. Perinuclear(P)-ANCA was detected with high sensitivity and specificity in renal vasculitis without WG, and the severity of necrotizing and crescentic nephritis in WG was correlated especially well with the C-ANCA titer. Detection of ANCA is considered clinically useful for the etiological differentiation of renal vasculitis, suggesting the possibility that C-ANCA may be involved in the onset of vasculitis of the glomerular capillary vessels in WG. The presence of C-ANCA and cytokines (IL-1 beta and TNF-alpha) is important in the pathogenesis of vasculitis and GN in WG.     

Pathogenesis of primary systemic vasculitides (I): ANCA-positive vasculitides

The pathogenesis of different types of systemic vasculitis positive for antineutrophil cytoplasmic antibodies (ANCA) remains incompletely understood. ANCA constitute a heterogeneous group of antibodies that are associated with different types of small-vessel vasculitis, including Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS). Anti-proteinase 3 ANCA are present in more than 90% of patients with systemic WG, and anti-myeloperoxidase (MPO) ANCA in 50-75% of those with MPA and 40-60 % of those with CSS. The pathogenic role of ANCA has been well documented in vivo: passive transfer of anti-MPO ANCA in an MPO knockout mouse model immunized with MPO is sufficient to induce the disease. In vitro, mouse and human anti-proteinase 3 ANCA can activate neutrophils primed with TNF-a and contribute to vasculitic lesions. T-cells are also involved: type 1 helper cytokines have been detected in tissue lesions of limited forms of WG, while type 2 helper cytokines have been identified in its systemic forms. Eosinophils may play a key role in the development of vasculitic lesions in CSS, although this remains to be proved.     

Antineutrophil cytoplasm antibody (ANCA) associated vasculitis

In 1982 we first reported the presence of antineutrophil cytoplasm antibodies (ANCA) in 8 patients with systemic vasculitis and segmental necrotizing glomerulonephritis. The results of long-term follow-up are described. Screening of 7,500 serum samples revealed positive ANCA in 9 additional patients with vasculitis. Eighty-eight other patients with vasculitis were ANCA negative, including 7 with microscopic polyarteritis nodosa (MPAN) and 8 with Wegener's granulomatosis (WG). Conversely, ANCA were never detected in the absence of vasculitis. Fourteen patients presenting with glomerulonephritis and ANCA were followed for a median of 6.3 years. Eleven patients had MPAN and 3 WG. Remissions were obtained with immunosuppressive therapy in all patients. Clinical relapse was associated with the reappearance of ANCA. Five-year survival was 89% and 5-year dialysis free survival was 77%. ANCA are specific markers for a sub-group of patients with vasculitis and are sensitive markers of disease activity. Glomerulonephritis associated with ANCA positive vasculitis has a favorable outcome with immunosuppressive therapy.     

Retrospective study of 97 ANCA-positive patients: epidemiologic and clinical spectrum

We analysed the clinical profile of antineutrophil cytoplasmic antibodies (ANCA) positive patients in a retrospective study including all cases of ANCA positivity (determined by ELISA) from the Nephrology Clinic, Parhon University Hospital Iasi during the interval 1998-2003. There were 97 ANCA positive patients (mean age 43.7 ?18-75? years, female/male ratio 1.55), of whom almost two thirds had c-ANCA, almost one third p-ANCA, while 9 patients had both types of antibodies. The incidence was 22.5/pmp for the North-Eastern province of Romania. Just 19.3% from the suspected cases with ANCA-associated disease were positive for these antibodies. 47.7% had systemic vasculitis (10 with microscopic polyangiitis--MA, 6 with Wegener's granulomatosis--WG, 1 with Churg-Strauss angiitis, 29 with non-specific vasculitis--NSV). Twenty-seven (27.8%) had connective tissue disease--CTD (systemic lupus erythematosus, rheumatoid arthritis, polymyositis, systemic sclerosis, mixed connective tissue disease, and sarcoidosis), while in 5 cases ANCA were associated with other diseases. Nine cases presented with rapid progressive glomerulonephritis (RPGN) without signs of systemic involvement, and other ten with advanced chronic renal failure (CRF). The most frequent clinical manifestations involved the kidney (71%), the skin, the muscles and joints, and the cardiovascular system. CONCLUSIONS: ANCA positivity is associated with a wide spectrum of diseases, mostly with CTD and NSV. c-ANCA was predominantly seen in WG and advanced CRF, while p-ANCA was associated with MA. In nonspecific vasculitis and connective tissue diseases, both patterns were present. We recommend ANCA determination as a screening method in all cases with renal dysfunction and nephritic syndrome and/or with signs of systemic vasculitis and/or collagenosis.     

Clinical significance of autoantibodies against neutrophil cytoplasmic components in patients with renal disease

The diagnostic significance of anticytoplasmic autoantibodies (ANCA) was studied in 71 renal patients. The ANCA test was positive in 67% of patients with Wegener's granulomatosis (WG), in 35% of those with a simultaneous renal and respiratory tract disease but not diagnosed as WG and in 22% of patients with a renal disease associated with unspecific collagenosis/vasculitis. Among WG patients ANCA positivity clearly correlated with the presence of active renal disease. Interestingly, both ANCA-positive and -negative patients were encountered in the group with acute renal failure and acute extracapillary glomerulonephritis associated with diffuse pulmonary infiltrates. The diagnostic and clinical significance of the ANCA test in these cases remains for the present obscure. In the majority of the ANCA-positive renal patients with respiratory tract abnormalities, the antibodies showed diffuse cytoplasmic staining and were mostly of the IgG class, of both IgG and IgM classes in some cases and of IgG, IgM and IgA classes in 1 patient. In patients with unspecific vasculitis/collagenosis the level of ANCA was rather low, and the distribution of different isotypes resembled that of patients with respiratory symptoms. A certain isotype of ANCA or staining pattern did not mark out any clinicopathologic subgroup among the patients. Our findings indicate that the clinical picture of ANCA-positive patients varies considerably and the ANCA test may not be as specific a marker of WG as previously suggested.     

ANCA-negative pauci-immune renal vasculitis: histology and outcome.

BACKGROUND: Pauci-immune renal vasculitis with focal glomerular necrosis and crescent formation is usually associated with anti-neutrophil cytoplasmic antibodies (ANCAs). However, ANCA's are absent in up to 10% of cases, which constitutes a rarely studied variant of renal vasculitis. METHODS: This retrospective multicentre cohort study analyzed the presenting features, renal histology and outcome in 20 patients with pauci-immune crescentic necrotizing renal vasculitis in whom indirect immunofluorescence did not detect ANCA. RESULTS: Renal histology revealed a high percentage of active glomerular lesions (50%), mainly cellular crescents, 28% of them with glomerular necrosis. Chronic tissue damage with glomerulosclerosis (21%) and diffuse interstitial fibrosis (40%) was already present at diagnosis, more prominent than in historical PR3-positive patients. Infiltrates of polymorphonuclear neutrophils in glomerular capillary loops were observed in 40% of all biopsies, mainly in necrotic lesions. The subsets of interstitially infiltrating leukocytes similar to ANCA-associated disease. Microscopic polyangiitis was diagnosed in 17 patients, Wegener's granulomatosis in two and renal-limited vasculitis in one. The patients median disease extent index (DEI) of 5 (range 4-11) reflected a systemic vasculitis. ANCA-negative vasculitis was not associated with infection or malignancy. Renal outcome was correlated to DEI (P = 0.032) and serum creatinine at diagnosis (P = 0.04). The mortality rate was high (35%) and closely related to age above 65 years at diagnosis (P = 0.014). Conclusions. The histological findings and prognosis in ANCA-negative renal vasculitis are comparable with those of ANCA-positive disease. Our data underline the importance of the exact diagnosis in an active vasculitic disease process even in the absence of ANCAs.     

Human anti-neutrophil cytoplasm autoantibodies to proteinase 3 (PR3-ANCA) bind to neutrophils

BACKGROUND: Recently, the in vivo pathogenic role of anti-neutrophil cytoplasm autoantibodies (ANCA) in ANCA-associated vasculitis has been challenged by Abdel-Salam et al. In their report, they observed that ANCA directed against proteinase 3 (PR3) cannot bind to their target autoantigen PR3 on circulating neutrophils (PMN). Here we present evidence that human PR3-ANCA do specifically bind to PMN that express PR3 on their membrane. METHODS: PMN were isolated from donors showing bimodal membrane PR3 expression on their PMN (N= 3). TNFalpha-primed PMN or PMA-stimulated PMN were incubated with serum or plasma from PR3-ANCA-positive patients with Wegener's granulomatosis (WG) (N= 8) or healthy controls (N= 8). Binding of IgG in serum or plasma samples to PMN was assessed by indirect immunofluorescence. RESULTS: Binding of IgG in undiluted plasma or serum from PR3-ANCA-positive WG-patients to PMN was significantly increased compared to plasma or serum from healthy controls. Dilution of plasma and serum showed concentration-dependent binding of IgG. Double staining for PR3 and IgG demonstrated that IgG in plasma or serum from PR3-ANCA-positive patients only bound to those PMN that expressed PR3, and not to PMN that lacked PR3 expression on their membrane. CONCLUSION: PR3-ANCA in undiluted serum or plasma from PR3-ANCA-positive WG patients bind to TNFalpha- primed and PMA-stimulated PMN that express PR3 on their membrane. Therefore, the hypothesis that PR3-ANCA can bind and activate primed PMN is still the most attractive explanation for the contribution of PR3-ANCA to the pathogenesis of Wegener's granulomatosis.     

Antineutrophil cytoplasm antibody-stimulated neutrophil adhesion depends on diacylglycerol kinase-catalyzed phosphatidic acid formation

Patients with certain forms of systematic vasculitis, such as Wegener's granulomatosis, have circulating antineutrophil cytoplasmic antibodies (ANCA). These inappropriately stimulate circulating neutrophils adhere to and thereby obstruct small vessels. This, together with ANCA-induced degranulation and an oxidative burst, leads to local tissue damage. The signaling pathways that are activated by ANCA IgG are distinct from those that are involved in normal neutrophil activation. This study shows that diacylglycerol kinase is selectively activated by ANCA and that the generated phosphatidic acid is responsible for promoting neutrophil adhesion, in part through integrin activation. The data presented point to diacylglycerol kinase alpha as a novel but selective target for the development of drugs to treat this potentially fatal disorder.     

The Diagnostic and Prognostic Significance of ANCA

Antineutrophil cytoplasmic antibodies (ANCA) constitute a family of autoantibodies directed against various components of the neutrophil cytoplasm. Their identification and association with vasculitis and rapidly progressive glomerulonephritis has led to considering these diseases as possible autoimmune disorders. In addition, ANCAs constitute a diagnostic tool and a guideline for therapy during follow-up. Originally identified by Davies et al. in 1982 in 8 patients who had necrotizing glomerulonephritis but no immune deposits or systemic vasculitis (1), ANCA are now regarded as a serological marker for active pauci-immune necrotizing and crescentic glomerulonephritis, either in their renal-limited form or associated with systemic vasculitis such as Wegener's granulomatosis (WG), microscopic polyangütis (mPA), and Churg-Strauss syndrome (CSS) (2-9). The usefulness of ANCA detection for the diagnosis of these forms of vasculitis is now established but its usefulness on follow-up remains disputed (10-13). Two major ANCA antigens have already been identified. Proteinase 3 (PR3) in a serine protease of 29 kDa initially identified by Kao and producing a cytoplasmic staining pattern termed cANCA by indirect immunofluorescence (IIF) (14,15). Myeloperoxidase (MPO) is another myeloid lysosomal enzyme producing an artefactual perinuclear staining of ethanol-fixed neutrophils termed pANCA (2,16). Both are localized in the azurophilic granules of neutrophils and monocytes, are translocated to the cell surface during cell activation (17), and are able to interact directly with ANCA. Despite this common location, MPO and PR3 are associated with a broad spectrum of clinical conditions.     

Prostatic involvement in Wegener's granulomatosis

Two cases of Wegener's granulomatosis presenting with prostatic involvement are described and compiled with the five previously detailed cases. Each of these patients presented with obstructive symptoms, proteinuria, leukocyturia, and hematuria. The urinary sediment normalized with treatment of the underlying granulomatous vasculitis. Wegener's granulomatosis is a rare cause of prostatic obstructive symptoms, but should be considered whenever the relatively unusual entity of granulomatous prostatitis is diagnosed. One patient was initially treated exclusively with trimethoprim-sulfamethoxazole (TMP-SMX). He responded, but noted recurrence during the 15th month of treatment. We also report on this patient's antineutrophil cytoplasmic antibody (ANCA) titers, which correlated with clinical assessment and predicted recurrence 2 months before elevation of the Westergren sedimentation rate (WSR) and clinical diagnosis.