Antineutrophil Cytoplasm Antibody: Positivity and Clinical Correlation

Téllez, Goitybell Martínez; Rives, Bárbara Torres; Velázquez, Suchiquil Rangel; Rodríguez, Vicky Sánchez; Ríos, María Antonia Ramos; Smith, Lisset Evelyn Fuentes

doi:10.1016/j.reumae.2014.02.010

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…As depicted in Table 2, the nuclear homogenous pattern (AC1) is most frequently linked to possible pANCA interference (31.5% cases) compared to other patterns like speckled (11.1%), DFS70 (10.3%), and centromere (6.7%). Such pattern correlation tallies well with earlier works [16][17][18]. Some studies did not include pattern information, unlike ours [17].…”

Section: Discussionsupporting

confidence: 93%

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Interference of Antinuclear Antibody (ANA) in Indirect Immunofluorescence Assay (IIFA)-Based Perinuclear Antineutrophil Cytoplasmic Antibody (pANCA) Interpretation

Deka

Kalita

Rekha

et al. 2022

Autoimmune Diseases

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Background. Indirect immunofluorescence assay (IIFA) based on antineutrophil cytoplasmic antibody (ANCA) testing is a commonly employed test for diagnosing autoimmune vasculitis. Antinuclear antibody (ANA) can give rise to a false interpretation of perinuclear-ANCA (pANCA) in ethanol-fixed granulocyte substrates. Analytical interference could frequently occur in setups where ethanol-fixed substrates are used alone. Here, we intend to investigate this ANA interference in pANCA interpretation. Methods. In this retrospective study, we studied anti-MPO-negative but ANA-positive and pANCA (IIFA based) samples. We also correlated immunoblot results (where data were available) and checked the association between grades of blot positivity (an indicator of the concentration of ANA) and frequency of pANCA interpretation. Data were analyzed by appropriate statistical techniques (Chi-square and kappa statistics). Results. About 19.2% of ANA blot (ENA-blot) positive samples displayed a pANCA positive pattern in the ethanol-fixed substrate, while this positivity in ENA-blot negatives was 6.5%. In positive ANA-IIFA samples, about 14.7% yielded pANCA patterns (on ethanol fixed substrates). Out of this, nuclear homogenous pattern yielding samples gave the highest frequency pANCA, that is, in 31.5% followed by speckled (11.1%), DFS (10.3%), and centromere (6.7%).The association of the nuclear homogenous pattern was statistically significant. Conclusions. ANA-positive results may interfere with the interpretation of pANCA as observed in ANA-IIFA and ENA-blot positive samples. ANA-IIFA patterns like nuclear homogenous may strongly associate this pANCA interpretation. This can help laboratories perform ANCA testing more effectively, ruling out ANA interference in ANCA screening.

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Section: Discussionsupporting

confidence: 93%

“…Such pattern correlation tallies well with earlier works [ 16 – 18 ]. Some studies did not include pattern information, unlike ours [ 17 ]. We also analyzed immunoblot results ( Table 1 ), which was unique about our current work.…”

Section: Discussionmentioning

confidence: 99%

Interference of Antinuclear Antibody (ANA) in Indirect Immunofluorescence Assay (IIFA)-Based Perinuclear Antineutrophil Cytoplasmic Antibody (pANCA) Interpretation

Deka

Kalita

Rekha

et al. 2022

Autoimmune Diseases

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“…An important group of primary vasculitis comprises ANCA-associated vasculitis (AAVs) [10,11] characterized by circulating ANCAs directed against MPO and PR3 proteins of neutrophil granules. Neutrophil cell death is implicated in the pathophysiology of AAVs.…”

Section: Introductionmentioning

confidence: 99%

NETosis Secondary to the Use of Levamisole-Adulterated Cocaine: A Likely Underlying Mechanism of Vasculopathy

Osorio,

Velásquez,

Vargas

et al. 2024

Journal of Toxicology

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Background. Since 2010, several cases of a new vasculopathy induced by the use of levamisole-adulterated cocaine (LAC) have been reported. This vasculopathy is characterized by retiform purpura, earlobe necrosis, multisystem compromise, and multiple autoantibodies. Given its similarity to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, LAC-associated vasculopathy is postulated to be mediated by pathophysiologic processes resulting from neutrophil cell death by NETosis, a phenomenon previously described in ANCA vasculitis. This study tries to establish the presence of NETosis induced by cocaine, levamisole, or both. Methodology. Neutrophils were isolated from the peripheral blood of healthy controls by Ficoll-Hystopaque density gradient centrifugation followed by dextran sedimentation. Cell viability and purity were evaluated by flow cytometry after staining with PI/DiOC6 and labeling with fluorescent anti-CD45/anti-CD3 monoclonal antibodies (mAbs), respectively. Neutrophils were exposed to levamisole, cocaine, a cocaine-levamisole mixture, and sera pools from healthy controls and patients with LAC-associated vasculopathy. NETosis was then assessed by flow cytometry after staining cells with Sytox Green, Hoechst-33342, and fluorescent antineutrophil elastase (NE) and antimyeloperoxidase (MPO) mAbs. In addition, NETosis was morphologically confirmed by fluorescence microscopy. Proinflammatory cytokine levels in culture supernatants and reactive oxygen species (ROS) synthesis were determined by flow cytometry. The involvement of calcium and muscarinic receptors in cell death induction was evaluated in parallel experiments carried out in the presence of 1,2-bis (o-aminophenoxy) ethane-N, N, N′, N′-tetraacetic acid (BAPTA) and hyoscine butylbromide (HBB), their respective inhibitors. Results. Cocaine, levamisole, and a cocaine-levamisole mixture induced neutrophil cell death. DNA/MPO extrusion and cell morphology patterns were consistent with NETosis. Neither proinflammatory cytokines nor ROS behaved as proNETotic factors. Preliminary results suggested that muscarinic receptors and calcium-dependent signals were involved in LAC-induced NETosis. Conclusions. Cocaine, levamisole, and a cocaine-levamisole mixture can induce NETosis through mechanisms involving muscarinic receptors and calcium-dependent pathways.

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“…Антитела, ассоциированные с ферментом миелопероксидазой, в 70 % случаев встречаются при ЭГПА. Поэтому выявление ANCA класса IgG с помощью реакции непрямой иммунофлюоресценции рекомендуется использовать в качестве базового скринингового теста [7][8][9].…”

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Eosinophilic Granulomatosis With Polyangiitis

Drobysheva,

Demin

2023

SMV

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Introduction. Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as allergic granulomatosis (Churg-Stross syndrome), in the modern sense is a necrotizing multisystem vasculitis of predominantly small vessels associated with hyperproduction of antineutrophil cytoplasmic antibodies (ANCA), peripheral blood hypereosinophilia. Although the most frequently involved are the respiratory organs (rhinosinusitis, bronchial asthma, pulmonary infiltrates), EGPA affects any organs and systems (heart, kidneys, gastrointestinal tract, nervous system, skin, joints, etc.) which makes its diagnosis difficult. Aim. To present an observation of a difficult-to-diagnose clinical case of eosinophilic granulomatosis with polyangiitis. Materials and methods. The analysis of clinical, laboratory, special testing of the patient was carried out. Results. Diagnosis of EGPA in this patient was difficult. Fever up to 40°C, papulo-necrotic skin eruptions on upper and lower extremities, trunk; weight loss; multiple organ involvement of heart, lungs, kidneys, liver; positive hemoculture with isolation of Staph. haemoliticus, and from skin lesions of Staph. epidermidis – all these served as a reason to suspect staphylococcal sepsis with possible infectious endocarditis and prescribe antimicrobial therapy which was ineffective. Progression of the disease with worsening clinical manifestations, detection of blood eosinophilia (18%), positive ANCA on immunological examination, eosinophilic and lymphohistiocytic infiltration around microvessels on histological examination of the musculocutaneous flap allowed the diagnosis of EGPA to be verified. Pulse chemotherapy with cyclophosphamide and medium doses of methylprednisolone led to regression of the disease manifestations in the patient. Conclusion. The course of EGPA can include life-threatening conditions (acute myocardial infarction and pulmonary hemorrhage). Timely diagnosis and standards of active chemotherapy expand possibilities of managing this severe group of patients.

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Antineutrophil Cytoplasm Antibody: Positivity and Clinical Correlation

Cited by 5 publications

References 22 publications

Interference of Antinuclear Antibody (ANA) in Indirect Immunofluorescence Assay (IIFA)-Based Perinuclear Antineutrophil Cytoplasmic Antibody (pANCA) Interpretation

Interference of Antinuclear Antibody (ANA) in Indirect Immunofluorescence Assay (IIFA)-Based Perinuclear Antineutrophil Cytoplasmic Antibody (pANCA) Interpretation

NETosis Secondary to the Use of Levamisole-Adulterated Cocaine: A Likely Underlying Mechanism of Vasculopathy

Eosinophilic Granulomatosis With Polyangiitis

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