scholarly journals Myeloperoxidase-antineutrophil Cytoplasmic Antibodies (MPO-ANCA) and Proteinase 3-ANCA without Immunofluorescent ANCA Found by Routine Clinical Testing

2015 ◽  
Vol 42 (5) ◽  
pp. 847-852 ◽  
Author(s):  
Deepak A. Rao ◽  
Kevin Wei ◽  
Joseph F. Merola ◽  
William R. O’Brien ◽  
Samuel U. Takvorian ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Systemic Vasculitis ◽  
Real Life ◽  
Retrospective Chart Review ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Antibody Assays ◽  
Missed Diagnosis ◽  
Inflammatory Bowel ◽  
New Diagnosis ◽  
Antibody Tests

Objective.Concurrent testing for serum antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IF) and by antiproteinase 3 (PR3)/antimyeloperoxidase (MPO) antibody assays may identify patients with PR3-ANCA or MPO-ANCA despite a negative IF (IF-negative MPO/PR3-positive); however, the significance of this result is not clear. We sought to determine whether IF-negative, MPO/PR3-positive results identified any cases of clinically meaningful systemic vasculitis at our institution.Methods.We conducted a retrospective chart review of all IF-negative, MPO/PR3-positive patients identified at our institution over a 2-year period.Results.Of the 2345 samples tested over 2 years, 1998 were IF-negative. Among these IF-negative samples, 49 samples (2.5%) derived from 38 patients tested positive for MPO-ANCA or PR3-ANCA. Only 1 IF-negative, MPO/PR3-positive patient was subsequently diagnosed with ANCA-associated vasculitis (AAV). Eleven IF-negative, MPO/PR3-positive patients (29%) had been previously diagnosed and treated for AAV, all with positive IF and antibody tests prior to treatment. Four patients had evidence of cutaneous vasculitis not attributed to AAV, while several of the remaining IF-negative, MPO/PR3-positive patients had other immunologic disorders, including systemic lupus erythematosus (5 patients) and inflammatory bowel disease (3 patients).Conclusion.In this real-life cohort assayed simultaneously by IF and multiplexed bead assays, the detection of MPO-ANCA or PR3-ANCA without a positive IF rarely led to a new diagnosis of systemic vasculitis, and was more likely to occur in the context of a non-vasculitic inflammatory condition. Our results suggest that concurrent IF and MPO/PR3 testing may be of limited use in preventing a missed diagnosis of new-onset AAV.

Yield of Screening Tests for Systemic Vasculitis in Young Adults with Ischemic Stroke

2018 ◽  
Vol 80 (5-6) ◽  
pp. 245-248 ◽  
Author(s):  
Cindy W. Yoon ◽  
Hee-Kwon Park ◽  
Joung-Ho Rha
Keyword(s):  
Young Adults ◽  
Ischemic Stroke ◽  
Lupus Erythematosus ◽  
Screening Test ◽  
Systemic Vasculitis ◽  
Young Patients ◽  
Anticardiolipin Antibody ◽  
Screening Tests ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
High Yield

Systemic vasculitis, which can involve the brain, may be one of the causes of stroke in young adults; therefore, a test panel for systemic vasculitis is considered for some young stroke patients. However, little is known about this test’s yield as a screening test in young adults with ischemic stroke. We evaluated the yield of a panel for systemic vasculitis as a screening test in young patients with ischemic stroke. Consecutive patients aged 18–45 years with ischemic stroke between January 2010 and December 2017 were included. They all underwent screening tests for systemic vasculitis including rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibodies, anticardiolipin antibody, lupus anticoagulant, anti-DNA antibody, and anti-Ro/SSA and La/SSB antibodies. Among 3,593 consecutive patients with acute ischemic stroke during the study period, 198 (5.5%) were aged 18–45 years. Only 4 patients (2.0%) were diagnosed with systemic vasculitis; 2 had systemic lupus erythematosus, 1 had Sjogren’s syndrome, and 1 had Churg-Strauss syndrome. Vasculitis panel screening in every young ischemic stroke patient is not of high yield unless a vasculitic process is highly suspected based on other systemic symptoms or signs of vasculitis. Screening should be targeted toward persons with clinical suspicion.

Autoimmune Disease (AD) in Patients with Myelodysplastic Syndrome (MDS): A Retrospective Single Institution Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4736-4736
Author(s):  
Jeyanthi Ramanarayanan ◽  
Alan N. Baer ◽  
Minoo Battiwalla ◽  
Laurie A. Ford ◽  
Meir Wetzler ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Systemic Vasculitis ◽  
Multiorgan Failure ◽  
Clinical Manifestations ◽  
Response To Therapy ◽  
Entire Cohort ◽  
Double Stranded Dna ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Autoimmune disease (AD) can manifest uncommonly either at the time of diagnosis of MDS or during its course. When present, AD generally responds to immunosuppressive therapies, but cytopenias and immunosuppression associated with MDS compromise delivery of these therapies. Few studies have investigated the impact of co-existing AD on the course and outcome of patients with MDS. Our objective was to evaluate the clinical manifestations, laboratory characteristics, response to therapy and survival of MDS patients with AD. Records of patients evaluated at Roswell Park Cancer Institute with pathologically demonstrated MDS between 1993 and 2003 (n=277) were reviewed and patients with evidence of AD were identified. Patients with laboratory abnormalities without disease manifestations were excluded, as were patients with therapy-related MDS following treatment for AD. 13 patients (4%) were identified with co-existing MDS and AD. The initial presentation was AD in 6 (46%) and MDS in 4 (31%), while 3 patients (23%) had near-simultaneous diagnoses of both conditions. The spectrum of AD in these patients included systemic vasculitis in 3 patients, systemic lupus erythematosus in two and rheumatoid arthritis, temporal arteritis, cryoglobulinemia, aphthous stomatitis, pyoderma gangrenosum, inflammatory bowel disease, erythema nodosum and Evans syndrome in one patient each. Anti-double stranded DNA (levels ≥ 40.0 u/ml; normal range 0.0–3.5u/ml), ANA (≥1:160), cold agglutinins, low C3 and elevated ESR (≥100mm/hr) were the serological abnormalities detected at the time of AD diagnosis. Eleven of 13 patients were female, and median age at diagnosis of MDS was 65 years, while the entire cohort was 44% female (p=0.005) and had a median age of 71 yrs at diagnosis. FAB subtypes were RA (n=7), RAEB (n=3), CMMoL (n=2) and RARS (n=1). Cytogenetics were normal in 5 patients; abnormalities in the other 8 patients included −7, +8, and del(5q). The median survival of patients from diagnosis of MDS was 48 months and the survival from diagnosis of AD was 46 months. Known causes of death in 6 patients included sepsis, intracranial hemorrhage, lung cancer and transplant-associated multiorgan failure. Based on this study, AD occurs in 4% of MDS patients, predominantly affects female patients, and has heterogeneous clinical manifestations.The pathobiologic implication of the occurrence of AD at the same time or after the diagnosis of MDS is that the dysplastic clone might be responsible for the induction of immune dysregulation.

Analytical and diagnostic accuracy of the EliA™ automated enzyme fluoroimmunoassay for antineutrophil cytoplasmic autoantibody detection

2004 ◽  
Vol 42 (10) ◽  
Author(s):  
Danilo Villalta ◽  
Elio Tonutti ◽  
Marilina Tampoia ◽  
Nicola Bizzaro ◽  
Wolfgang Papisch ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Lupus Erythematosus ◽  
Clinical Performance ◽  
Systemic Vasculitis ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Quantitative Detection ◽  
High Positive Correlation ◽  
Analytical Accuracy ◽  
Assay Precision ◽  
Good Diagnostic Accuracy

AbstractAnti-proteinase 3 antineutrophil cytoplasmic antibodies (PR3-ANCA) and anti-myeloperoxidase antibodies (MPO-ANCA) are considered important serological markers for several forms of idiopathic systemic vasculitis. The aim of the study was to verify the analytical and clinical performance of a new automated enzyme fluoroimmunoassay, the EliA system, for PR3-ANCA and MPO-ANCA detection.For this purpose the sera of 52 consecutive well-defined patients with a clinical diagnosis of Wegener’s granulomatosis (WG) (n = 29) or microscopic polyangiitis (MPA) (n = 23), and 70 controls suffering from connective tissue disease (25 systemic lupus erythematosus, 25 Sjögren’s syndrome and 20 rheumatoid arthritis) were tested for PR3-ANCA and MPO-ANCA with the EliA assay (Pharmacia Diagnostics, Freiburg, Germany). For comparison purposes, the same sera were also tested by indirect immunofluorescence, another direct immunometric assay (Varelisa, Pharmacia Diagnostics) and a capture PR3-ANCA (Wieslab AB, Lund, Sweden) method.Both the EliA PR3-ANCA and MPO-ANCA assays showed between- and within-assay precision of < 10%. The dilution test gave straight lines (rThere was a high positive correlation between the EliA and Varelisa methods for quantitative detection of MPO-ANCA levels (rIn conclusion, the EliA MPO-ANCA and PR3-ANCA methods provide good diagnostic accuracy and excellent analytical accuracy, which, in association with the practicality of the automated EliA system, make this method a useful tool for the diagnosis of ANCA-associated vasculitides.

scholarly journals Clinical Comparison of QUANTA Flash dsDNA Chemiluminescent Immunoassay with Four Current Assays for the Detection of Anti-dsDNA Autoantibodies

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Maria Infantino ◽  
Francesca Meacci ◽  
Chelsea Bentow ◽  
Peter Martis ◽  
Maurizio Benucci ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Control Group ◽  
Immunofluorescence Test ◽  
Indirect Immunofluorescence Test ◽  
Crithidia Luciliae ◽  
Dsdna Antibody ◽  
Antibody Assays ◽  
Chemiluminescent Immunoassay ◽  
Antibody Tests ◽  
Good Agreement

Introduction. The objective of the present study was to compare QUANTA Flash dsDNA, a chemiluminescent immunoassay (CIA) on the BIO-FLASH, a rapid-response chemiluminescent analyzer, to three other anti-dsDNA antibody assays and to Crithidia luciliae indirect immunofluorescence test (CLIFT). Methods. In the first part of the study, 161 samples, 61 from patients suffering from systemic lupus erythematosus (SLE) and 100 from a disease control group, were tested by QUANTA Flash dsDNA CIA, QUANTA Lite dsDNA SC ELISA, BioPlex 2200 multiplex flow immunoassay (MFI), ImmuLisa dsDNA ELISA, and NOVA Lite CLIFT. A second cohort of 69 SLE patients was then tested by QUANTA Flash dsDNA and CLIFT to expand the study. Results. The overall qualitative agreements varied between 77.0% (NOVA Lite CLIFT versus QUANTA Lite) and 89.4% (ImmuLisa versus NOVA Lite CLIFT). The clinical sensitivities for the anti-dsDNA antibody tests varied from 8.2% (NOVA Lite CLIFT) to 54.1% (QUANTA Lite), while the clinical specificities varied from 88.0% (BioPlex 2200) to 100.0% (NOVA Lite CLIFT). Good correlation was found between QUANTA Flash dsDNA and NOVA Lite CLIFT. Conclusion. Significant variations among dsDNA methods were observed. QUANTA Flash dsDNA provides a good combination of sensitivity and specificity for the diagnosis of SLE and good agreement to CLIFT.

scholarly journals AB0511 INTERNATIONAL CONSENSUS ON ANCA TESTING AND INTERPRETATION BEYOND SYSTEMIC VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1553.2-1553
Author(s):  
S. Moiseev ◽  
J. W. Cohen Tervaert ◽  
Y. Arimura ◽  
D. Bogdanos ◽  
C. Elena ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
Lupus Erythematosus ◽  
Inflammatory Bowel Diseases ◽  
Systemic Vasculitis ◽  
Connective Tissue Diseases ◽  
Idiopathic Interstitial Pneumonia ◽  
Small Vessel Vasculitis ◽  
Research Support ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:ANCA can be detected in sera from patients with autoimmune, inflammatory, infectious or neoplastic diseases.Objectives:To issue a Consensus Statement on ANCA testing and interpretation beyond systemic vasculitis.Methods:This Statement was prepared by a group of experts, based on the results of a comprehensive search in PubMed.Results:In certain settings beyond systemic vasculitis, ANCA may have diagnostic, clinical, and/or prognostic relevance. Testing for PR3- and MPO-ANCA by specific immunoassays should be performed in any patient with clinical features suggesting ANCA-associated vasculitis and in patients with anti-GBM disease and idiopathic interstitial pneumonia. Routine ANCA testing is not recommended in patients with connective tissue diseases (CTD), autoimmune liver diseases, inflammatory bowel diseases, infections, and/or malignancy unless there is evidence for small vessel vasculitis. ANCA testing by specific immunoassays may be useful in patients with rheumatoid arthritis, systemic sclerosis or primary Sjögren’s syndrome who have kidney disease with a nephritic sediment or in patients with systemic lupus erythematosus if a kidney biopsy shows prominent necrotizing and crescentic lesions or proliferative lupus nephritis. ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1, who do not have conventional disease-related autoantibodies, or in patients with inflammatory bowel diseases in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn’s disease. In these cases, ANCA should be tested by indirect immunofluorescence since target antigens are not well characterized. ANCA against bactericidal/permeability-increasing protein may be a biomarker for deteriorating lung function and a poor prognosis in patients with cystic fibrosis.Conclusion:ANCA testing is clinically relevant not only in patients with manifestations suggesting systemic vasculitis, but also in patients with certain other disorders, particularly in patients with anti-GBM disease or idiopathic interstitial pneumonia.Disclosure of Interests:Sergey Moiseev Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Jan Willem Cohen Tervaert: None declared, Yoshihiro Arimura: None declared, Dimitrios Bogdanos: None declared, Csernok Elena: None declared, Jan Damoiseaux: None declared, Marc Ferrante: None declared, Luis Felipe Flores-Suárez: None declared, Marvin Fritzler: None declared, Pietro Invernizzi: None declared, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, J. Charles Jennette: None declared, Mark Little: None declared, Stephen P. McAdoo: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Charles D. Pusey: None declared, Antonella Radice: None declared, Alan D. Salama: None declared, Judith Savige: None declared, Mårten Segelmark: None declared, Yehuda Shoenfeld: None declared, Renato Alberto Sinico: None declared, Maria Jose Rego de Sousa: None declared, Ulrich Specks: None declared, Benjamin Terrier: None declared, Athanasios Tzioufas: None declared, Severine Vermeire: None declared, Ming-hui Zhao: None declared, Xavier Bossuyt: None declared

scholarly journals P477 Italian real-life study evaluating the long-term effectiveness of vedolizumab for the treatment of inflammatory bowel disease: the elderly cohort

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S419-S422
Author(s):  
D Pugliese ◽  
G Privitera ◽  
A Armuzzi
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Real Life ◽  
Treatment Persistence ◽  
Diagnosis Of Cancer ◽  
Inflammatory Bowel ◽  
New Diagnosis

Abstract Background Vedolizumab (VDZ) is the first biological therapy for Inflammatory Bowel Disease (IBD) tested, in pivotal trials, on patients up to 80 years old and has usually been presented as a safer choice in frail patients. However, real-world data on the effectiveness and safety of VDZ in elderly (≥ 65 years) are scarce. The aim of this study is to explore the effectiveness and safety of VDZ in a large real-life cohort of elderly IBD patients, with a 2 years follow-up. Methods The Long-term Italian Vedolizumab Effectiveness (LIVE) study included CD and UC patients started on VDZ from April 2016 to June 2017 at 40 centres of the Italian Group for the study of inflammatory bowel disease (IG-IBD). Patients were prospectively followed-up to June 2019. Co-primary endpoints were to evaluate cumulative VDZ treatment persistence and safety. Results Of 966 patients, 174 (18%; 81 CD, 93 UC) were ≥ 65 years old at enrolment. Mean disease duration at baseline was 10.9 years ± SD10 (CD 12.5 ± 11, UC 9.6 ± 9). VDZ was used as a first biologic therapy in 78 patients (44.8%). 25 patients (14.4%) had a history of previous cancer. The majority of CD patients had a stricturing behaviour (45, 55.6%) and had already undergone surgery (41, 49.4%). 48 UC patients (51.6%) had extensive colitis. Moderate-to-severe endoscopic activity was present in 80% of CD and in 92% of UC, according to SES-CD and endoscopic Mayo score, respectively. Cumulative VDZ treatment persistence at 12 and 24 months was 71.8% (71.6% CD and 72.0% UC) and 54% (54.2% CD and 53.8%% UC), respectively. 52.9% (40 CD; 52 UC), 4.0%, 3.5%% and 2.9% of patients were on concomitant steroids at baseline, 6, 12, and 24 months, respectively. Clinical remission at 12 and 24 months was achieved in 28.7% (31 CD and 29 UC) and in 31.6% (25 CD and 30 UC) of patients. Mean C-reactive protein was 15.6 mg/l ± SD 20 (CD 15.9 ± 21; UC 15.2 ± 19) at baseline and dropped to 8.4 mg/l ± 10 (CD 8.0 ± 8, UC 8.9 ± 11) at 12 months and to 5.9 mg/l ± 6 (CD 5.8 ± 5, UC 6 ± 7) at 24 months. Dose escalation was necessary for 20.3% and 24.7% of patients within the first 12 and 24 months. 44 adverse events were reported: 16 infections.,6 new diagnosis of cancer/dysplasia (2 colon, 1 kidney, 1 prostate, 1 lung, 1 melanoma), 4 arthritis, 3 skin rash, 2 drug-induced cholestasis,11 miscellaneous. 11 patients (6.3%) underwent VDZ withdrawal because of adverse events (6 new diagnosis of cancer/dysplasia; 4 infections; 1 cholestasis). One patient died for pneumonia complications. Conclusion In this preliminary analysis of the largest reported real-world cohorts of elderly IBD patients treated with VDZ, up to 55% of patients persisted on therapy after two years; an acceptable safety profile was observed throughout the entire follow-up period.

Borderline positive antineutrophil cytoplasmic antibodies (ANCA)-PR3/MPO detection in a large cohort tertiary center: lessons learnt from a real-life experience

2018 ◽  
Vol 56 (6) ◽  
pp. 947-953 ◽  
Author(s):  
Abdulla Watad ◽  
Nicola L. Bragazzi ◽  
Kassem Sharif ◽  
Boris Gilburd ◽  
Yarden Yavne ◽  
...  
Keyword(s):  
Life Experience ◽  
Laboratory Data ◽  
Real Life ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Female Ratio ◽  
Tertiary Center ◽  
Male To Female ◽  
Antibody Tests

Abstract Background: Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) are the best strategies for antineutrophil cytoplasmic antibodies (ANCA) detection. In a minority of subjects, ELISA-based ANCA testing may result in a borderline positive titre. Therefore, we assessed the clinical significance of such a result. Methods: This is a retrospective study, which included all subjects screened for ANCA subtypes (myeloperoxidase (MPO) or proteinase-3 (PR3)) with subsequent identification of borderline positive results, as determined by ELISA and retested using IIF. The demographic, clinical and laboratory data of subjects with borderline positive ANCA test results were extracted from their medical records. Results: A total of 14,555 PR3/MPO-ANCA tests were performed with ELISA during the study period (2006–2016). Of the 14,555 PR3-ANCA antibody tests that were performed, 94 were borderline positive (titre 0.9–1.1), and of 14,555 MPO-ANCA antibody tests, 43 were borderline positive (titre 0.9–1.1). The male-to-female ratio was 1:1.08 and the mean age was 50.95±21.79 years. Four MPO-ANCA (9.30%) and 11 PR3-ANCA (11.70%) antibody borderline samples resulted positive on IIF testing. Subjects with borderline positive MPO-ANCA were found to have a poorer outcome in terms of renal failure and the requirement of dialysis. Conclusions: Subjects with borderline positive MPO-ANCA and positive p-ANCA (IIF) seem to have a less favorable outcome. Physicians should be aware of these findings and possibly perform a closer follow-up and routine screening for these subjects.

scholarly journals Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

2021 ◽  
Vol 10 (4) ◽  
pp. 853
Author(s):  
Giuseppe Privitera ◽  
Daniela Pugliese ◽  
Gian Ludovico Rapaccini ◽  
Antonio Gasbarrini ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Current Knowledge ◽  
Real Life ◽  
Response To Therapy ◽  
Significant Heterogeneity ◽  
Intestinal Damage ◽  
Biological Therapies ◽  
Early Markers ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

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