Anti-neutrophil Cytoplasmic Antigen Research Articles

Characteristics and prognosis of acute renal failure on dialysis in ANCA vasculitis

Renal involvement in ANCA (Anti Neutrophil Cytoplasmic Antigen) vasculitis is common and is associated with increased mortality with a significant risk of progression to end-stage renal disease. The aim of this study is to investigate the epidemiological, clinicopathological, therapeutic and evolutionary characteristics of patients with ANCA vasculitis with acute renal injury, and to evaluate the impact of haemodialysis in the acute phase on mortality and renal recovery. Secondary objectives are to investigate other risk factors that impact on overall and renal survival. 31 patients were included; the mean follow-up time was 30 months. The mean age was 68.52 years, and the sex ratio 0.72. All patients had acute renal failure, with histology revealing a mixed form in 45% of cases and a sclerotic form in 12.9% of cases. Pulmonary involvement was found in 58% of cases. 71% of patients had ANCA with anti-myeloperoxydase specificity, and 25.8% anti-proteinase3 specificity. 32.2% of patients required haemodialysis, of which 60% were weaned. As initial treatment, 58.1% of patients received cyclophosphamide and 35.5% rituximab. The relapse rate was 6.5%. Infectious and cardiovascular complications affected more than half of the patients. The mortality rate was 19.35%. Comparing the two groups of patients dialysed in the acute phase and not dialysed, it appears that the overall and renal mortality was comparable. The progression to end-stage renal failure was higher in the dialysis patients. In a multivariate study, the presence of chronic kidney disease in the history and pulmonary involvement were associated with higher mortality.

Hearing Prognosis of Otitis Media with Antineutrophil Cytoplasmic Antigen Associated Vasculitis (OMAAV) using Contrast-Enhanced Magnetic Resonance Imaging

Hearing Prognosis of Otitis Media with Antineutrophil Cytoplasmic Antigen Associated Vasculitis (OMAAV) using Contrast-Enhanced Magnetic Resonance Imaging

Genetic regulation of CD177 – A receptor presenting anti-neutrophil cytoplasmic antigen proteinase 3

Genetic regulation of CD177 – A receptor presenting anti-neutrophil cytoplasmic antigen proteinase 3

Cocaine-Levamisole Thrombotic Vasculopathy

The syndrome of cocaine-levamisole thrombotic vasculopathy is a tetrad of cutaneous manifestations, arthralgia, leukopenia, and positive antineutrophil cytoplasmic antigen (ANCA). Cocaine is cut with levamisole to potentiate its euphoric effects. However, along with this are the adverse reactions of levamisole such as fatal agranulocytosis, flu-like symptoms, and cutaneous thrombotic vasculopathy. High index of suspicion is needed for its diagnosis. This article will review on its toxicities, especially its prothrombotic effects.

Association of ANCA-associated vasculitis-rheumatoid arthritis overlap syndrome in four patients: Rituximab may be the right choice?

Objectives: There have been few reports on the association of rheumatoid arthritis (RA) with anti-neutrophil cytoplasmic antigen (ANCA)-associated systemic vasculitides. Methods: Here we present four cases of RA overlapping with Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS). All these cases had both the diagnosis of RA and that of ANCA-associated vasculitis. Results: After we tried corticosteroids, multiple immunosuppressive drugs, sometimes plasmapheresis, rituximab was introduced to 3 out of 4 cases. Rituximab therapy was found to be effective in these three overlap cases. In the fourth case, rituximab was and will be considered; however, the patient has not given consent. Conclusion: To our knowledge, this is the first report on RA+CSS association. Common pathogenic background, such as genetic predisposition and ANCA may account for the development of RA+vasculitis overlaps. In DMARD-refractory cases, such as the ones presented here, biologics, especially rituximab may be highly effective.

Syndrome of Cocaine-Levamisole-Induced Cutaneous Vasculitis and Immune-Mediated Leukopenia

We describe 4 patients who presented with palpable purpura, arthralgia or arthritis, leukopenia, and antineutrophil cytoplasmic antigen (ANCA) positivity most likely as a result of a hypersensitivity reaction to cocaine-levamisole induced vasculopathy. Cases were seen and reviewed in both the inpatient consult service and the outpatient clinics at Rhode Island Hospital from August 2009 to August 2010. Clinical characteristics as well as pertinent laboratory parameters were also reviewed and corroborated with a review of the present literature. We describe 3 cases of cocaine-levamisole-related cutaneous vasculitis with or without associated neutropenia, and 1 case of severe neutropenia with oral mucosal ulceration. Further serologic studies revealed maximum titers of ANCA mostly in a perinuclear pattern. Antimyeloperoxidase tested negative or mildly elevated in our cohort. Three patients with neutropenia had positive antigranulocyte IgM antibody. Nonsteroidal anti-inflammatory drugs were effective as first-line treatment for joint pain. The use of colchicine and systemic corticosteroid was employed to manage severe and persistent skin lesions. Cocaine-levamisole-related cutaneous vasculitis with leukopenia is a diagnosis of exclusion, but this diagnosis should be strongly considered in patients with a history of cocaine abuse who present with a tetrad of cutaneous manifestations consisting of palpable purpura or bullae with ear involvement, arthralgias, leukopenia, and positive ANCA in high titers and negative Antimyeloperoxidase, when other infectious or idiopathic vasculitic entities have been excluded.

Chronic Lymphocytic Leukemia-Associated Cholangiopathy

1University of Birmingham Medical School, Birmingham, United Kingdom; 2Department of Pathology, Calgary Laboratory Services; 3Division of Hematology and Hematological Malignancies; 4Liver Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta Correspondence: Dr Mark G Swain, Division of Gastroenterology, Health Research Innovation Center, Room 4AA20, 3280 Hospital Drive, Northwest, Calgary, Alberta T2N 4Z6. Telephone 403-220-3719, fax 403-210-9146, e-mail swain@ucalgary.ca Received for publication May 9, 2011. Accepted May 16, 2011 CASE PRESENTATION A 41-year-old woman with untreated low-grade B-cell chronic lymphocytic leukemia (CLL), diagnosed by peripheral blood flow cytometry nine months previously (white blood cell count 14.7×109/L; lymphocytes 10.4×109/L), was referred to the University of Calgary Liver Unit (Calgary, Alberta) with abnormal serum levels of liver enzymes: alkaline phosphatase 138 U/L to 204 U/L (normal lower than 115 U/L); aspartate aminotransferase 42 U/L (normal lower than 32 U/L); alanine aminotransferase 53 U/L (normal range 1 U/L to 40 U/L); and gamma-glutamyl transferase 115 U/L to 187 U/L (normal lower than 35 U/L). She was asymptomatic and her medical history consisted only of hypothyroidism treated with thyroxine. She was taking no other regular medications or herbal supplements. She consumed one to two standard alcoholic beverages per week. The physical examination was normal (body mass index 21 kg/m2). A screen for metabolic liver diseases was negative, as were tests for viral hepatitis. Antinuclear antibody was positive at a titre of 1:5210, with a speckled homogeneous pattern (NSP1). Rheumatoid factor was also positive (85 kU/L; normal lower than 20 kU/L). Anti-smooth muscle, antineutrophil cytoplasmic antigen, immunoglobulin A antitransglutaminase and antimitochondrial antibodies were negative. Serum immunoglobulin levels were all normal. Ultrasound of the liver was normal. Percutaneous liver biopsy was performed. The biopsy core (2 cm) included 17 portal areas; seven were expanded by a monotonous infiltrate composed predominantly of small lymphocytes. There was no parenchymal infiltrate. Bile ducts within lymphocyte-infiltrated portal spaces were pushed toward the periphery (Figure 1). Of note, four bile ducts showed distinct lymphocytic infiltration within the biliary epithelium (cholangiopathy), resulting in a significant narrowing of the bile duct lumen (Figures 2 and 3). The lymphocytic infiltrate was further characterized by immunohistochemical staining for the following: CD3, CD5, CD10, CD20, CD23, Bcl-2, cyclin-D1 and Ki67. The results of the immunological staining profile were classical for CLL (the Bcl-2 staining is shown in Figure 4).

ANCA-associated vasculitides—lessons from the adult literature

Anti-neutrophil cytoplasmic antigen antibody (ANCA)-associated disease is a rare manifestation of primary systemic vasculitis in paediatric patients but one that carries significant morbidity, potential long-term disability and early mortality. It therefore requires a high index of suspicion, targeted investigation, prompt treatment and long-term follow-up with specialist input at every stage. The well-recognised diversity and overlap in clinical, laboratory and histopathological features of the ANCA-associated systemic vasculitides continue to hamper accurate diagnosis, confounding epidemiological data and necessitating a blanket approach to treatment, which is largely extrapolated from studies in adult patients and carries significant side-effects. Herein we summarise current knowledge of the epidemiology, pathogenesis, principal manifestations, investigation and evidence-based management, extrapolated from adult studies, of these disorders. We also discuss recent efforts towards classification of the childhood vasculitides that emphasise the value of histological diagnosis. Progress in our understanding of the pathophysiology underlying ANCA-associated disease should lead to targeted, safer and more effective therapies for these conditions. Nonetheless, many questions remain outstanding, and academic paediatricians face real challenges in identifying and collating the few cases they encounter into study cohorts. Meeting this challenge will require international collaboration, not only among paediatricians but also with the specialists taking over care of these patients as they reach adulthood.

Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in normal human polyspecific IgG for therapeutic use and in the remission sera of patients with systemic vasculitis

Anti-neutrophil cytoplasmic antigen (ANCA) activity was inhibited in 15 out of 21 sera from patients with acute systemic vasculitis following incubation with normal polyspecific IgG for therapeutic use (IVIg). ANCA antibodies reacted with IVIg through idiotypic-anti-idiotypic interactions, as shown in competitive binding assays using F(ab')2 fragments from IVIg and affinity chromatography of ANCA IgG on Sepharose-bound F(ab')2 fragments from IVIg. Co-incubation of sera from patients with acute systemic vasculitis with paired autologous remission stage sera also resulted in inhibition of ANCA activity in acute sera. Remission sera contain IgM and IgG capable of interacting with beta and or alpha idiotypes of ANCA IgG from acute sera. Anti-idiotypic IgM may account for the lack of expression of ANCA activity in whole serum from patients in remission from systemic vasculitis, which were found to contain high titres of ANCA IgG. These observations suggest that remission of systemic vasculitis is associated with the generation of anti-idiotypes against autoantibodies rather than the suppression of production of ANCA autoantibodies. IVIg may modulate the activity of systemic vasculitis in vivo.

Intravenous immunoglobulin improves clinical outcome in Churg-Strauss syndrome

▴ Danieli MG, Cappelli M, Malcangi G, et al . Long term effectiveness of intravenous immunoglobulin in Churg-Strauss syndrome. Ann Rheum Dis2004;63:1649–54 [OpenUrl][1][Abstract/FREE Full Text][2] Churg-Strauss Syndrome (CSS) is a necrotising vasculitis of medium and small sized vessels clinically characterised by asthma, eosinophilia, and systemic vasculitis associated with circulating antibodies to antineutrophil cytoplasmic antigen (ANCA). The standard treatment of this condition comprises corticosteroids and, in severe cases, cytotoxic drugs. However, this treatment protocol is associated with a high relapse rate and significant drug … [1]: {openurl}?query=rft.jtitle%253DAnnals%2Bof%2Bthe%2BRheumatic%2BDiseases%26rft.stitle%253DAnn%2BRheum%2BDis%26rft.issn%253D0003-4967%26rft.aulast%253DDanieli%26rft.auinit1%253DM%2BG%26rft.volume%253D63%26rft.issue%253D12%26rft.spage%253D1649%26rft.epage%253D1654%26rft.atitle%253DLong%2Bterm%2Beffectiveness%2Bof%2Bintravenous%2Bimmunoglobulin%2Bin%2BChurg-Strauss%2Bsyndrome%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fard.2003.015453%26rft_id%253Dinfo%253Apmid%252F15547090%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=annrheumdis&resid=63/12/1649&atom=%2Fthoraxjnl%2F60%2F3%2F225.atom

Influence of Plasma Exchange on Serum Levels of Cytokines and Adhesion Molecules in ANCA-Positive Renal Vasculitis

Background: Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active antineutrophil cytoplasmic antigen (ANCA)-positive renal vasculitis. Plasma exchange (PE) may influence the activity of vasculitis not only by removing pathogenic autoantibodies, but also by lowering the serum levels of circulating cytokines. Methods: Serum levels of IL-1β, IL-1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 patients with active ANCA-positive renal vasculitis (5 patients with Wegener’s granulomatosis, WG, and 5 patients with microscopic polyangiitis, MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained at the beginning and at the end of the 1st, 3rd and 5th PE and in samples of filtrate obtained during the same PE. Results: In comparison with controls, patients with ANCA had higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1 before the 1st PE. Serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 were increased in patients with MPA, and the serum levels of all the cytokines and adhesion molecules measured in patients with WG were increased. At the end of the PE course there were decreases in the serum levels of IL-1ra and VCAM-1 in ANCA patients and IL-1ra and ICAM-1 in WG patients. Single PE in ANCA patients led only to a decrease in serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change in serum levels of IL-1β and IL-8, and the serum levels of IL-1ra and IL-6 even increased at the end of a single PE, in spite of high levels of all cytokines and adhesion molecules in the plasma filtrate. Conclusion: Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by a PE course. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with the synthetic membrane. The insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.