Antineutrophil Cytoplasmic Antibody Positive Patients Research Articles

Impact of different ANCA serotypes on the long-term outcome of ANCA-associated vasculitis patients

Objectives To investigate the clinical features and long-term outcomes of Chinese anti-neutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (AAV) patients with different ANCA serotypes. Methods Two hundred and twenty-four AAV patients from January 2010 to June 2021 were divided into myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA groups. Clinical and long-term outcomes were compared. Results In this study, the average follow-up was 46.4 months (range 0.3–188.4 months). One hundred and seventy-seven (79.0%) patients were MPO–ANCA-positive and 47 were PR3–ANCA-positive; the mean age of MPO–ANCA positive patients at diagnosis was elder than that of PR3–ANCA positive patients (67.0 vs. 60.0 years, p = .004). Among PR3–ANCA-positive patients, ear, nose and throat symptoms were more common (p = .014). Between two ANCA serotypes, there were no differences in complement 3 (C3), Birmingham vasculitis activity score (BVAS), five-factor score (FFS) or other organ involvements. For all AAV patients, the overall survival rates at one, three and five years were 80.0%, 67.0% and 56.4%, respectively. The cumulative relapse-free rates of one, three and five years were 89.5%, 76.4% and 68.4%, respectively. The survival of AAV patients was unaffected by the ANCA serotype (p = .23). The ANCA serotype also had no effect on either disease relapse (p = .20) or remission rates (p = .10). In our study, PR3–ANCA patients showed a better long-term survival, as the 5-year survival rate and the 5-year relapse-free survival rate of PR3–ANCA patients were 60.7% and 76.9%, while that of MPO–ANCA patients were 55.2% and 65.8%, respectively. Rather than ANCA serotype, younger patients with milder kidney involvement and lower disease assessment scores (BVAS and FFS) might be more relevant to better prognosis. Conclusions The likelihood of induced remission, patient survival or disease recurrence is all unaffected by ANCA serotypes. A better prognosis is seen in younger patients with milder kidney involvement and lower BVAS/FFS scores.

Comparison of Clinico-pathologic features and outcomes of ANCA negative and ANCA positive pauci immune crescentic glomerulonephritis: A single centre study.

Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.

PULMONARY FIBROSIS AND FOOT DROP: A CASE OF MICROSCOPIC POLYANGIITIS FOLLOWING IDIOPATHIC PULMONARY FIBROSIS (IPF) DIAGNOSIS

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Pulmonary fibrosis (PF) associated with antineutrophil cytoplasmic antibody (ANCA) is a rare but described diagnosis, with some patients meeting criteria for microscopic polyangiits (MPA). Conversion to ANCA-MPO positivity and MPA with vasculitic findings can lag behind the initial diagnosis of PF. CASE PRESENTATION: We present a case of a 75 year old man with a history of a bladder tumor and PF who presented to clinic with 6 months of worsening cough, fatigue, weight loss and neuropathy. His PF was initially diagnosed 1 year prior and considered idiopathic. At that time he had an abnormal CT chest, significantly decreased DLCO, positive ANA, and normal inflammatory markers. Approximately one year later he complained of progressive cough, fatigue and weight loss, and was hospitalized for anemia and leukocytosis with an unrevealing workup. He was prescribed antibiotics for Aeromonas pneumonia. He then presented to clinic where his physical exam was notable for mild tachypnea, left foot drop and right hand numbness. PFTs revealed a significant decline in vital capacity and DLCO. He was admitted and workup revealed CT chest with new infiltrates, an elevated ANA, elevated ESR/CRP and elevated ferritin. ANCA- MPO was positive. He underwent sural nerve and skeletal muscle biopsy which showed necrotizing vasculitis with fibrinoid necrosis, and he was started on high dose steroids. He improved and was discharged to home to start rituximab infusion as outpatient. DISCUSSION: Pulmonary fibrosis associated with ANCA vasculitis is rare and typically associated with MPA. Case studies have placed prevalence of ANCA positive PF from 2-14% of PF patients initially considered idiopathic. Of those patients, about half had seroconversion/develop MPA after initial PF diagnosis. CT imaging for ANCA-MPO patients may be indistinguishable IPF on imaging with a UIP pattern of fibrosis. The pathogenesis of ANCA-MPO associated fibrosis is unclear, but possibly related to recurrent alveolar hemorrhage, direct damage from neutrophils or ANCA induced by a pulmonary inflammatory process. ANCA positive PF patients are more likely to be treated with steroids and immunosuppression including cyclophosphamide or ritxumab. These treatments may be useful in early disease, but likely have limited efficacy in late stage/fibrotic disease. Patients with MPA and PF have a clinical progression similar to patients with IPF, with worse survival compared to MPA patients without PF. Not all PF patients with ANCA-MPO positivity develop systemic vasculitis, however, clinicians should be on alert for signs and symptoms of systemic disease as early intervention could prevent progression. CONCLUSIONS: It is important to consider ANCA vasculitis both at the time of diagnosis of pulmonary fibrosis and later in a patient’s clinical course. Reference #1: Casares MF, Gonzales MF, Caputo F, Bottinelli Y, Zamboni M. Microscopic polyangiitis associated with pulmonary fibrosis. Clin Rheumatol 2015 34:1273-1277. Reference #2: Kagiyama N, Takayanagi N, Kanauchi T, et al. Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patients with idiopathic pulmonary fibrosis.BMJ Open Respiratory Research 2015;2:e000058. Reference #3: Tzelepis GE, Kokosi M, Tzioufas A, et al. Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis. Eur Resp J 2010; 36:116-121 DISCLOSURES: No relevant relationships by Samantha Parker, source=Web Response

Efficacy and safety of rituximab in the treatment of eosinophilic granulomatosis with polyangiitis

IntroductionEosinophilic granulomatosis with polyangiitis (EGPA) is a subset of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis with distinct pathophysiological mechanisms, clinical features and treatment responses. Rituximab is a licensed therapy for...

Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus.

BackgroundThe clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated.ObjectivesThis study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients.MethodsA hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test.ResultsForty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%).Study limitationsThe sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias.ConclusionsThe level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

Pathogenesis of diseases with antineutrophil cytoplasmic antibody and its clinical significance

Objective To investigate the pathogenesis of diseases with antineutrophil cytoplasmic antibody(ANCA) and its diagnostic value in primary small vessel vasculitis. Methods 57 patients with serum ANCA positive were involved in this study, and ELISA was employed to assay anti-MPO.Patients with ANCA positive, anti-MPO positive and/or anti-PR3 positive were involved in group A. Patients with ANCA positive, anti-MPO negative and anti-PR3 negative were involved in group B. X2 was used to analyze the differences between the two groups. Results The etiology of 57 ANCA positive patients included primary small vessel vasculitis (20 cases, 35.1%), non inflammatory connective tissue disease(19 cases, 33.3%), non connective tissue disease(18 cases, 31.6%). A group of primary small vessel vasculitis accounted for 58.6%, which was significantly higher than 10.7% of the B group (χ2=14.354, P<0.01); while the B group of non inflammatory connective tissue disease accounted for 50%, which was significantly higher than 17.2% of the A group (χ2=6.879, P<0.01). Conclusion ANCA should be found in many kinds of diseases, so combined detection of anti-MPO and anti-PR3 should be employed to improve the diagnosis specificity in primary small vessel vasculitis.Furthermore, non vessel vasculitis connective tissue disease should be excluded in patients with ANCA positive, anti-MPO and anti-PR3 negative. Key words: Antineutrophil cytoplasmic antibody; Myeloperoxidase antibody; Anti-PR3; Vasculitis

Immune Complex-positive Glomerulonephritis in Antineutrophil Cytoplasmic Antibody-positive Patients

ABSTRACTUveitic glaucoma consists one of the most serious complications of intraocular inflammation and, despite its rarity, is considered as one of the leading causes of preventable loss of vision worldwide. It has been associated with a wide spectrum of inflammatory diseases, but its pathogenesis is still not fully comprehended. It appears that the type of inflammation, the steroid-response and the anatomical alterations of the anterior chamber play a pivotal role. To our knowledge, the mechanisms may be both acute and chronic. The main targets of the treatment are to control the inflammation and reduce the intraocular pressure (IOP). The management of glaucoma associated with uveitis remains an extremely challenging condition for ophthalmologists. The successful treatment of uveitic glaucoma is inextricably correlated with prompt and immediate therapeutic decisions. Very often a solid collaboration between clinicians from different specialties may be required for treating the underlying disease.Further understanding of its pathogenesis can indicate therapeutic targets and may lead to the development of new and more efficient therapeutic approaches. New glaucoma surgical modalities may ameliorate the prognosis after surgical intervention, but this calls for further evaluation. This study aims to highlight the complexity of uveitic glaucoma analyzing the main pathogenetic mechanisms and the correlations with the inflammatory response.How to cite this articleKalogeropoulos D, Sung VCT. Pathogenesis of Uveitic Glaucoma. J Curr Glaucoma Pract 2018;12(3):125-138.

Diagnosing ANCA-associated vasculitis in ANCA positive patients: A retrospective analysis on the role of clinical symptoms and the ANCA titre.

Currently no validated diagnostic system for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is available. Therefore, diagnosing AAV is often challenging. We aimed to identify factors that lead to a clinical diagnosis AAV in ANCA positive patients in a teaching hospital in The Netherlands.In this study, all patients that tested positive for ANCA proteinase 3 (PR3) and/or myeloperoxidase (MPO) between 2005 and 2015 were analysed. Patients with a clinical diagnosis of AAV were compared with patients without a clinical diagnosis of AAV. Clinical symptoms and laboratory variables at presentation, including the ANCA titre, were collected for both patients with and without AAV. Clinical and laboratory variables related with AAV were investigated, using multivariable logistic regression.Two hundred thirty seven consecutive patients with a positive ANCA were included, of whom 119 were clinically diagnosed with AAV. Of the 118 ANCA positive patients without AAV, 87 patients had an alternative diagnosis, including inflammatory bowel disease (n = 24), other rheumatic diseases (n = 23), infection (n = 11), malignancy (n = 4), and other diagnoses (n = 25). In a multivariable regression model, a high ANCA titre (odds ratio [OR] 14.16, 95% confidence interval [CI] 6.93-28.94) and a high number of affected organ systems (OR 7.67, 95% CI 3.69-15.94) were associated with AAV.MPO and PR3 ANCA can be positive in a variety of diseases that mimic AAV. A higher ANCA titre and multiple affected organ systems may help to discriminate between AAV and other systemic illnesses in anti-PR3 and anti-MPO positive patients. A diagnostic scoring system incorporating these factors should be considered.

ASSESMENT OF ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY POSITIVITY PATTERN IN VARIOUS DIAGNOSTIC GROUPS

In present study, frequency and patterns of anti-neutrophil cytoplasmic antibody (ANCA) and its` relationship with clinic situations were investigated in samples which were referred by miscellaneous diagnosis. Presence of ANCA were retrospectively studied on 1668 samples. All sera were first evaluated by indirect immunofluorescence technique (IIF). Then, samples with positive florescence were evaluated to determine specific antigens by enzyme-linked immunosorbent assay (ELISA) which implies proteinaseâ€q3 and myeloperoxidase. Samples in which none of these antigens were detected were reevaluated by ELISA ANCA profile test which implies less common antigens such as cathepsin G, lactoferrin, elastase and bactericidal permeability-increasing protein. Positive staining was found in 320 (19.2%) of 1668 serum samples by IIF technique. Samples in which specific antigens were found by ELISA were obtained from 49 patients. Of the 49 ANCA positive patients, anti-myeloperoxidase antibody was found in 42.9%, whereas anti-proteinaseâ€q3 antibody in 49%. Both anti-myeloperoxidase and anti-proteinaseâ€q3 antibodies were detected in 8.1% of these patients. Identifying presence of ANCA as well as determining patterns and antibodies directed against specific antigens will improve its` diagnostic significance.

Anti-proteinase 3 antibodies in diffuse systemic sclerosis (SSc) with normotensive renal impairment: is it suggestive for an overlapping between SSc and idiopathic vasculitis?

OBJECTIVE: To test the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic sclerosis (SSc) and to verify a possible association of ANCA with normotensive renal involvement in SSc. PATIENTS AND METHODS: 51 patients affected by SSc, 35 with diffuse scleroderma (dSSc) and 16 with limited scleroderma (lSSc), were tested for ANCA by indirect immunofluorescence (IIF) on human ethanol and formalin-acetone-fixed granulocytes (before and after DNase treatment), by conventional enzyme linked immuno-sorbent assay (ELISA) and by capture-ELISA. RESULTS: Six out of 51 selected SSc patients had ANCA by IIF (11.7%) and five presented a perinuclear/nuclear atypical ANCA pattern. In all cases we only found anti-proteinase3 (aPR3) antibodies. All ANCA positive patients had diffuse form of SSc (17.1%), all were anti-Scl70 positive (aScl70), five patients had proteinuria, three had microscopic haematuria. All ANCA positive patients were normotensive with normal renin plasma levels, the mean erythrocyte sedimentation rate (ESR) was higher in this group compared to the other SSc patients. CONCLUSIONS: Our study shows that aPR3 is not rare in dSSc. According to the clinical and serological findings and to the recent literature, we can hypothesise that when ANCA are found in SSc, an overlapping of scleroderma with systemic necrotizing vasculitis should be suspected.

Prevalence of antineutrophil cytoplasmic antibody positivity in patients with Hodgkin’s and non-Hodgkin lymphoma: a single center experience

Hematological malignancies are associated with the release of different autoantibodies and rheumatological manifestations. Systemic vasculitides are rare in hematological malignancies, and antineutrophil cytoplasmic antibodies (ANCA) have not been described sufficiently in hematological malignancies. In this present prospective study, we examined the prevalence of ANCA and related disease in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients in the southeast region of Turkey. We examined 119 patients with previously or newly diagnosed NHL and 60 patients with HL for the presence of ANCA and related autoimmune diseases between December 2002 and February 2007. ANCA positivity was detected in only 8 patients (4.4%); and all of these ANCA positivities were detected in patients in the HL group (13.3%); p-ANCA positivity was detected in 6 patients (3.3%); and c-ANCA positivity was detected in 2 patients (1.1%). There was statistically significant difference between patients with HL and NHL in terms of p-ANCA (p = 0.001) but none in c-ANCA (p = 0.111) positivity. None of the ANCA positive patients had vasculitides or rheumatic manifestations. In addition, we did not detect any ANCA positivity in the NHL group. In conclusion, ANCA positivities were detected only in HL patients; but we did not detect the association between ANCA positivities and rheumatic manifestations or vasculitis and also the different treatment responses in HL patients.

HLA-DR in Brazilian Patients with Polyarteritis Nodosa (PAN) and Microscopic Polyangiitis (MPA)

The aim of this study was to evaluate the frequency and clinical associations of HLA-DR alleles in Brazilian Caucasian patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA). We evaluated 29 Caucasian patients with vasculitis classified as PAN or MPA according to the American College of Rheumatology (ACR) 1990 Criteria, Chapel Hill Consensus Conference (CHCC) nomenclature for vasculitis and EULAR recommendations for conducting clinical studies in systemic vasculitis. HLA-DR alleles were typed using polymerase chain reaction-amplified DNA, hybridized with sequence-specific low resolution primers. DNA obtained from 59 Caucasian healthy blood donors were used as control. In order to evaluate if a specific HLA may have influence on the clinical profile of those diseases, we also divided the patients according to Birmingham vasculitis score (BVAS) and Five-Factors Score (FFS) at the time of diagnosis. Increased frequency of HLA-DRB1*16 (p= 0.023) and DRB4*01 (p= 0.048) was found in patients with higher disease activity at the time of diagnosis (BVAS ≥ 22). Patients with less severe disease (FFS = 0) had a higher frequency of HLA-DRB1*03 (p= 0.011). Patients with gastrointestinal tract involvement had significantly increased frequency of HLA-DRB1*11 or B1*12 (p= 0.046), B1*13 (p= 0.021) and B3 (p= 0.008). In contrast, patients with renal disease, had higher frequency of DRB1*15 or DRB1*16 (p= 0.035) and B5 (p= 0.035). In the subgroup of patients with MPA, increased frequency of HLA-DRB1*15 was found in patients with BVAS ≥ 22 (p= 0.038) and FFS ≥ 1 (p= 0.039) suggesting that this allele is associated with more aggressive disease. Antineutrophil cytoplasmic antibodies (ANCA) negative MPA patients had significantly increased frequency of HLA-DRB1*11 or DRB1*12 when compared to ANCA positive patients (p= 0.023). Our results suggest that HLA-DR alleles may influence PAN and MPA clinical expression and outcome and that in MPA they participate in the mechanisms involved in the development to ANCA.

HLA-DR in Brazilian patients with polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA).

The aim of this study was to evaluate the frequency and clinical associations of HLA-DR alleles in Brazilian Caucasian patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA). We evaluated 29 Caucasian patients with vasculitis classified as PAN or MPA according to the American College of Rheumatology (ACR) 1990 Criteria, Chapel Hill Consensus Conference (CHCC) nomenclature for vasculitis and EULAR recommendations for conducting clinical studies in systemic vasculitis. HLA-DR alleles were typed using polymerase chain reaction-amplified DNA, hybridized with sequence-specific low resolution primers. DNA obtained from 59 Caucasian healthy blood donors were used as control. In order to evaluate if a specific HLA may have influence on the clinical profile of those diseases, we also divided the patients according to Birmingham vasculitis score (BVAS) and Five-Factors Score (FFS) at the time of diagnosis. Increased frequency of HLA-DRB1*16 (p = 0.023) and DRB4*01 (p = 0.048) was found in patients with higher disease activity at the time of diagnosis (BVAS ≥ 22). Patients with less severe disease (FFS = 0) had a higher frequency of HLA-DRB1*03 (p = 0.011). Patients with gastrointestinal tract involvement had significantly increased frequency of HLA-DRB1*11 or B1*12 (p = 0.046), B1*13 (p = 0.021) and B3 (p = 0.008). In contrast, patients with renal disease, had higher frequency of DRB1*15 or DRB1*16 (p = 0.035) and B5 (p = 0.035). In the subgroup of patients with MPA, increased frequency of HLA-DRB1*15 was found in patients with BVAS ≥ 22 (p = 0.038) and FFS ≥ 1 (p = 0.039) suggesting that this allele is associated with more aggressive disease. Antineutrophil cytoplasmic antibodies (ANCA) negative MPA patients had significantly increased frequency of HLA-DRB1*11 or DRB1*12 when compared to ANCA positive patients (p = 0.023). Our results suggest that HLA-DR alleles may influence PAN and MPA clinical expression and outcome and that in MPA they participate in the mechanisms involved in the development to ANCA.

Valeur des anticorps anticytoplasme des polynucléaires neutrophiles dans la maladie de Horton

Purpose The relevance of antineutrophil cytoplasmic antibody (ANCA) during giant cell arteritis is not established. The purpose of our study was to estimate the ANCA frequency and their impact on disease course of giant cell arteritis. Methods Thirty patients were followed-up for giant cell arteritis and had a detection of ANCA. Results Nine patient had positive ANCA (30%). These patients had no significant differences regarding clinical and biological data or number of relapses in comparison with patients having negative ANCA testing. However, the relapse occurred earlier in the presence of ANCA (six months versus 31.5 months). Conclusion In giant cell arteritis, detection of ANCA seems predictive of a premature relapse and should be associated with an acute monitoring of ANCA positive patients.

Immunologic Markers as Potential Predictors of Systemic Autoimmune Disease in Patients with Idiopathic Scleritis

To determine the clinical value of serological testing in patients with idiopathic scleritis. Retrospective case series. Medical records of patients with scleritis seen at an institutional referral center over an 11-year period were reviewed. Of 119 patients with scleritis seen at the University of Illinois Uveitis Clinic, 91 (76.5%) patients had no known etiology at initial presentation. Seventy of the 91 patients were tested for rheumatoid factor (RF), 19 (27.1%) of whom had a positive result. Ten (52.6%) of these RF positive patients were subsequently diagnosed with rheumatoid arthritis (RA) during a mean follow-up of 10.6 months (range, zero to 72 months), whereas only one of 51 (2.0%) RF negative patients developed RA, producing an odds ratio for developing RA in RF positive patients of 55.6 (95% confidence interval (CI) 7.8 to 369.8, P=.00001). Of the 70 patients who were tested for anti-neutrophil cytoplasmic antibody (ANCA), seven (10.0%) tested positive. Three (42.9%) of the ANCA positive patients subsequently developed Wegener granulomatosis (WG), whereas only two of 63 ANCA negative patients (3.2%) developed WG during a mean follow-up of 8.4 months (range, zero to 72 months). The odds ratio for developing WG in patients with idiopathic scleritis and a positive ANCA screen compared with a negative ANCA was 22.9 (95% CI 3.4 to 154.2, P=.006). The likelihood of patients with idiopathic scleritis developing RA and WG was increased if they had a positive RF or ANCA, supporting the role of immunologic marker testing in patients who present without systemic disease.

Clinical features and outcomes of hyperthyroidism patients positive in propylthiouracil-induced antineutrophil cytoplasmic antibody

To analyze the clinical features and outcomes of hyperthyroidism patients positive in propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA). The clinical data, including the clinical manifestations, treatment, and outcomes of 45 PTU-induced ANCA positive patients with hyperthyroidism were prospectively studied. Seventeen of the 45 patients had clinically evident vasculitis and 28 of the 45 patients were not complicated by vasculitis. In the vasculitis group, 13 patients (76.5%) had renal involvement manifested by hematuria, proteinuria, and renal insufficiency. 7 of them (41.2%) had lung involvement and 6 of them had hemoptysis. Perinuclear ANCA (p-ANCA) was detected in all 17 patients and 16 of them (94.1%) were anti-myeloperoxidase antibodies (MPO-ANCA) positive. PTU was discontinued in all 17 patients and the treatment was switched over to methimazole (MMI) in 6 patients. Four patients with severe organ involvement received prednisone and immunosuppressant for 6 to 12 months. No relapse or death occurred during the follow-up period (8 to 60 months with a median of 30 months). All the 17 patients achieved clinical remission except for two that developed end stage renal disease due to late diagnosis. 27 of the 28 patients without vasculitis (96.4%) were p-ANCA positive and 14 of them (50.0%) were MPO-ANCA positive. PTU treatment was discontinued in 24 patients and switched over to MMI treatment in 15 patients, and 4 patients continued to take low dose PTU. No vasculitis manifestation occurred during the follow-up period (3 to 36 months with a median of 20 months). However, the ANCA titer declined slowly in most patients in both groups. PTU treatment should be discontinued without delay in the PTU-induced ANCA positive patients with hyperthyroidism. Treatment can be switched over to MMI when necessary. Patients with severe organ involvement should receive prednisone and immunosuppressant. No vasculitis relapse is found during the follow-up after withdrawal of PTU. However, ANCA may keep positive for a long time.

Clinical characteristics of propylthiouracil (PTU) induced antineutrophil cytoplasmic antibodies positive cases; analysis of a case of PTU-induced ANCA positive patients with hyperthyroidism

To study the clinical characteristics of propylthiouracil (PTU) induced antineutrophil cytoplasmic antibodies (ANCA) positive cases and increase the awareness of PTU induced ANCA positive vasculitis (APV). The clinical data of nine cases with positive ANCA induced by PTU in Peking Union hospital since 2000 were analyzed and literature review was conducted. (1) Nine patients with hyperthyroidism, at a mean age of 33.1 (16 approximately 51), who were treated with PTU for a mean period of 32.4 months (3 approximately 84); (2) Sera from nine cases were ANCA positive, and autoantibodies from six tested cases could recognize not only MPO, but also PR3, HLE, BPI and LF; (3) Six cases with high titer perinuclear ANGA (pANCA) (> or = 1:1280) were diagnosed APV and all had renal involvement (five confirmed by renal biopsies), three cases with low titer pANCA (< or = 1:320) had little clinical manifestations of vasculitis; (4) Eight patients stopped taking PTU when positive ANCA were noted. One case with APV got remission after stopping PTU, the other three APV were treated with glucocorticosteroid and immunosuppressive agents at meanwhile. Only one patient kept taking PTU for eighteen months without an increased titer of ANCA. PTU could induce production of ANCA. High titer of ANCA might suggest existence of APV and the titer would be associated with status of APV. Early withdrawal of PTU and administration of glucocorticosteroid and immunosuppressive agents based on renal pathology will greatly improve the prognosis.

Genetic and serological markers to identify phenotypic subgroups in a Dutch Crohn’s disease population

Background and aims. Both genetic and microbial factors seem to play a pivotal role in the aetiopathogenesis of Crohn’s disease. The CARD15 frameshift mutation might link host genetic factors and the indigenous microbial flora, since CARD15 expression is stimulated by peptidoglycan, thereby activating NF-κB. It is hypothesised that CARD15 mutation carriers have defective anti-microbial reactions, resulting in more penetrating lesions and antibody responses, which are now being used as highly specific markers for Crohn’s disease. The serological marker anti- Saccharomyces cerevisiae antibody directed against cell wall oligomannosidic epitopes has high specificity for Crohn’s disease. Perinuclear anti-neutrophil cytoplasmic antibodies have been found in a subgroup of Crohn’s disease patients, mostly with colonic involvement. Methods. We investigated the incidence of two CARD15 mutations (3020insC and 2722G > C), anti- S. cerevisiae antibody, and perinuclear anti-neutrophil cytoplasmic antibody in 108 (73F/35M) patients with Crohn’s disease with a mean duration of disease since diagnosis of 16 (1–41) years in relation to their phenotype, according to the Vienna classification. Results. The prevalence of CARD15 frameshift mutation was 21%. Of all patients, 62% were anti- S. cerevisiae antibody positive, and 9% had perinuclear anti-neutrophil cytoplasmic antibodies. The prevalence of both anti- S. cerevisiae antibodies and perinuclear anti-neutrophil cytoplasmic antibodies was higher in the mutation carriers compared to non-carriers. Remarkably, all patients with a CARD15 mutation and positive anti- S. cerevisiae antibody had ileal disease. Carriership of the mutation was significantly associated with penetrating behaviour of the disease and weakly associated with stricturing behaviour. Furthermore, anti- S. cerevisiae antibody was associated with ileal disease involvement. Finally, most perinuclear anti-neutrophil cytoplasmic antibody positive patients showed ulcerative-like behaviour of disease (by means of colonic localisation). Conclusions. Genetic and serologic markers might be useful in defining patient subgroups. This may result in a more accurate prediction of disease behaviour, prognosis and therapeutic approach.

Image analysis: a novel approach for the quantification of antineutrophil cytoplasmic antibody levels in patients with Wegener's granulomatosis

Rises in antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) have predictive potential for a relapse of Wegener's granulomatosis (WG). To assess the value of image analysis for monitoring ANCA levels, we measured PR3–ANCA in a cohort of PR3–ANCA positive patients with WG that were prospectively followed in our clinic and compared findings with other techniques. ANCA levels were measured serially by quantitative image analysis, titration in indirect immunofluorescence (IIF), two different directly coated antigen-specific enzyme-linked immunosorbent assays (ELISA), and a capture ELISA using a PR3-specific monoclonal antibody in 16 consecutive WG patients prior to a renal relapse, and in 16 age- and sex-matched patients with inactive WG. The positive predictive value (PPV) of an increase in ANCA titers by image analysis for relapse was 69% (11 of 16). The PPV of an increase in ANCA was 61% (11 of 18) by IIF, 71% (12 of 17) by a commercial direct ELISA, 63% (12 of 19) by in-house direct ELISA, and 75% (12 of 16) by capture ELISA. The negative predictive value (NPV) of the absence of an increase in ANCA titers by image analysis for relapse was 69% (11 of 16). The NPV of the absence of an increase in ANCA was 64% (9 of 14) by IIF, 73% (11 of 15) by a commercial direct ELISA, 63% (9 of 13) by in-house direct ELISA, and 75% (12 of 16) by capture ELISA. In conclusions, quantitative image analysis is a novel technique based on the principle of IIF to quantify ANCA levels in a single dilution in a patient sample. No major differences were observed between image analysis and the other techniques in their capacity to predict relapses of disease activity.

Effect of diagnostic delay on disease severity and outcome in glomerulonephritis caused by anti-neutrophil cytoplasmic antibodies.

To measure the time between onset of symptoms and intention to treat in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis; and to investigate the effect of any delay in diagnosis on disease severity at presentation and outcome. All ANCA positive patients with biopsy proven glomerulonephritis presenting in the North West Region over a consecutive period of 57 months were identified from the North West Glomerular Disease Registry. Sixty nine patients were identified and notes from 61 were reviewed. The 61 patients had a median diagnostic delay of 92 days. In only 12 patients had an ANCA test been performed prior to the nephrology referral. Thirty three patients had renal failure requiring dialysis within one week of admission and had a shorter delay (median 72 days) than those not requiring dialysis (median 132 days). None of the 28 patients with independent renal function at presentation required dialysis subsequently. Eighteen (55%) of those who required dialysis recovered independent renal function at three months and 13 (39%) had long term recovery. Both for patients who did and did not undergo dialysis, a longer delay was correlated with an increased percentage of sclerotic glomeruli at presentation. Patients with end stage renal failure had a median delay of 92 days, compared with one of 42 days in those who were dialysis independent at final follow up. Prolonged delay in diagnosis of ANCA associated glomerulonephritis is associated with an increased risk of end stage renal failure.