Anticytoplasmic Autoantibodies in the Diagnosis and Follow-Up of Wegener's Granulomatosis

Specks, Ulrich; Wheatley, Christine L.; McDonald, Thomas J.; Rohrbach, Michael S.; DeRemee, Richard A.

doi:10.1016/s0025-6196(12)65300-2

Cited by 247 publications

(69 citation statements)

References 14 publications

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“…The standard IIF technique for ANCA detection was performed using ethanol-fixed neutrophil cytospin preparations (23). Patient sera were evaluated using 1:4 and 1:16 dilutions, as previously described and validated (20,22,23).…”

Section: Methodsmentioning

confidence: 99%

Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine‐induced midline destructive lesions but not autoimmune vasculitis

Wiesner¹,

Russell²,

Lee³

et al. 2004

Arthritis & Rheumatism

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203

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Objective. Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine-induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL.Methods. HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme-linked immunosorbent assays using purified native HNE as target antigen.Results. Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty-seven percent of HNE ANCA-positive CIMDL sera were also PR3 ANCA-positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA-negative, as were sera obtained from healthy controls.Conclusion. Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA-associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.

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Section: Methodsmentioning

confidence: 99%

Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine‐induced midline destructive lesions but not autoimmune vasculitis

Wiesner¹,

Russell²,

Lee³

et al. 2004

Arthritis & Rheumatism

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203

136

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“…Ethanol-fixed cytospin preparations of human peripheral blood neutrophils, HMC-1, HMC-1NEC, HMC-1/PR3 and HMC-1/PR3-S176A cells were prepared and indirect immunofluorescence (IIF) was performed as described elsewhere [21].…”

Section: Immunofluorescence Biosynthetic Labeling and Immunoprecipitmentioning

confidence: 99%

“…To determine whether rPR3 expressed by HMC-1/ PR3 cells is recognized by c-ANCA, 40 consecutive serum samples that had previously been determined to be c-ANCA positive by standard IIF on neutrophil cytospin preparations [21] and control sera (5 normal, 5 anti-myeloperoxidase ANCA positive, 10 containing various patterns of ANA and 5 containing anti-mitochondrial antibodies) were obtained from the clinical laboratory. The samples were tested independently by three investigators by IIF on cytospin preparations of HMC-1/PR3 and HMC-1NEC cells, and in parallel for PR3-reactivity by commercial ELISA [34].…”

Section: Recognition Of Rpr3 By C-anca Seramentioning

confidence: 99%

Recombinant human proteinase 3, the Wegener's autoantigen, expressed in HMC‐1 cells is enzymatically active and recognized by c‐ANCA

Specks¹,

Fass²,

Fautsch³

et al. 1996

FEBS Letters

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We developed a stable expression system for conformationally intact recombinant human PR3 (rPR3) using the human mast cell line HMC-I. Like in U937 cells, the rPR3 is processed from a 34 kDa precursor to the 29 kDa mature form, primarily as the result of oligosaccharide trimming. The rPR3 binds [3H]DFP and hydrolyzes the snbstrate N-methoxysuccinylAla-Ala-Pro-Val-pNA. The enzymatic activity is inhibited by greater than 95% by al-PI. The rPR3 and the enzymatically inactive mutant rPR3-S176A are both packaged in granules. Thus, proteolytic autoprocessing is not required for PRYs targeting to granules. This rPR3 is the first to be recognized by most c-ANCA from WG patients and all anti-PR3 ANCA that were detected by standard anti-PR3 specific ELISA. This expression system for rPR3 represents a versatile tool for the analysis of its intraceHular processing, structure-function relationships and interaction with autoantibodies.

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“…El cuadro histológicoesflorido y típicosóloen el 15% de los casos (12). En su patogenia se involucra la presencia de anticuerpos antigránulos de los PMN en el suero de los pacientes (12,23,24). La práctica de esta técnica ha aumentado la sensibilidad del diagnóstico de la granulomatosis de Wegener a 85-98% (12).…”

Section: Discussionunclassified

Leishmaniasis mucosa y otras lesiones destructivas centrofaciales

Rodríguez¹,

Sarmiento²,

Hernández³

1994

biomedica

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ResumenVarias enfermedades producen lesiones del área centrofacial. Una de las más frecuentes en nuestro medio es la leishmaniasis destructivas mucosa. Como el INS es un centro de estudio de leishmaniasis, se atendieron pacientes o sus biopsias con afecciones del macizo centrofacial, primariamente remitidas con el diagnóstico clínico de leihsmaniasis mucosa. En un período de 7 años (1987)(1988)(1989)(1990)(1991)(1992)(1993), se estudiaron 134 biopsias de estos pacientes. El diagnóstico de leishmaniasis mucosa fue definitivo en 26 casos, por demostración del amastigote con la coloración de hematoxilina eosina y el mismo diagnóstico se estableció por patrón histopatológico solamente, en 27 casos. Una técnica inmunoenzimática para demostrar los amastigotes no fue satisfactoria. La perforación banal del tabique nasal (52 biopsias) es la.entidad que el clínico y el patólogo confunden con mayorfrecuenciacon la leishmaniasis mucosa. Otras entidades demostradas fueron la paracoccidioidomicosis (3), histoplasmosis (2), rinosporidiosis (2). esporotricosis (l), tuberculosis bucal (3), lepra leprornatosa (l), escleroma nasal (2), granulomatosis de Wegener (2), linfomas angiocéntricos (4), aspiración crónica de cocaína (l), y carcinoma escamocelular palatino (1).La biopsia, luego de la historia clínica, es el pilar esencial para identificar y manejar adecuadamente estas lesiones, que pueden originar destrucción facial grave, a veces letal, si no se dispone del diagnóstico preciso y del tratamiento oportuno. SUMMARYVarious illnesses produce lesions in the central facial area. One of the most frequently encountered in our environment is mucotaneous leishmaniasis. As the INS is a centre for the study of mucotaneous leishrnaniasis, patients or their biopsies are seen with diseases relating to the greater facial area, being remitted primarily with a diagnosis of mucotaneous leishmaniasis. In aperiod of 7 years (1 987-1993), 134 biopsies taken from these patients were studied. The mucotaneous leishmaniasis diagnosis was confirmed in 26 cases by staining with hematoxylin-eosin to reveal the presence of amastigotes and the same diagnosis was suggested solely by histopathology in another 27 cases.An immunoenzymetechnique toshow amastigote presence proved to be unsatisfactory. Commonplace perforation of the septum (52 biopsies) is most frequently confused by the physician and the pathologist as being mucotaneous leishmaniais. Other entities which were revealed were paracoccidioidomicosis (3), histoplasmosis (2), rhinosporidiosis

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Anticytoplasmic Autoantibodies in the Diagnosis and Follow-Up of Wegener's Granulomatosis

Cited by 247 publications

References 14 publications

Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine‐induced midline destructive lesions but not autoimmune vasculitis

Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine‐induced midline destructive lesions but not autoimmune vasculitis

Recombinant human proteinase 3, the Wegener's autoantigen, expressed in HMC‐1 cells is enzymatically active and recognized by c‐ANCA

Leishmaniasis mucosa y otras lesiones destructivas centrofaciales

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