The Syndrome of Lung Hemorrhage and Nephritis Is Usually an ANCA-Associated Condition

Niles, John L.; Böttinger, Erwin P.; Saurina, Guillermo; Kelly, Kay; Pan, Guo Li; Collins, A. Bernard; McCluskey, Robert T.

doi:10.1001/archinte.1996.00440040118013

Cited by 175 publications

(59 citation statements)

References 25 publications

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“…In patients with pulmonary silicosis and renal failure, a renal biopsy revealed a pauci-immune necrotizing crescentic glomerulonephritis in a number of studies (52-57). ANCA positivity was later confirmed in these patients (52,(57)(58)(59)(60)(61), who received a diagnosis of ANCA-associated glomerulonephritis (58,(62)(63)(64). Silica-induced ANCA-positive disease is often associated with a perinuclear (P-ANCA) staining pattern under indirect immunofluorescence and with antibodies directed against MPO (52,65).…”

Section: Silica and Vasculitismentioning

confidence: 97%

Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Wijngaarden¹,

Rijn²,

Hagen³

et al. 2008

Clinical Journal of the American Society of Nephrology

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The first description of what is now known as antineutrophil cytoplasmic autoantibody-associated necrotizing vasculitis appeared more than 140 yr ago. Since then, many aspects of the pathogenic pathway have been elucidated, indicating the involvement of antineutrophil cytoplasmic autoantibodies, but why antineutrophil cytoplasmic autoantibodies are produced in the first place remains unknown. Over the years, many hypotheses have emerged addressing the etiology of antineutrophil cytoplasmic antibody production, but no exclusive factor or set of factors can so far be held responsible. Herein is reviewed the most influential hypotheses regarding the causes of antineutrophil cytoplasmic antibody-associated vasculitis with the aim of placing in an epidemiologic background the different hypotheses that are centered on environmental and genetic influences.Clin J Am Soc Nephrol 3: 237-252, 2008237-252, . doi: 10.2215 A ntineutrophil cytoplasmic autoantibody (ANCA)-associated necrotizing vasculitis was probably first described in 1866 by Kussmaul and Maier (1) as "polyarteritis nodosa." It was not until the early 1930s when the first case of what was later named Wegener's granulomatosis (WG) was described (2). The disease was named after Friedrich Wegener, who described it as an entity in 1939 (3). In 1985, antibodies associated with the disease were detected and later became known as ANCA (4). WG is a systemic autoimmune disease that can cause damage in various organs. Later, microscopic polyangiitis (MPA) was distinguished as a separate ANCA-associated vasculitis. The disease-or its immunosuppressive treatment-can cause high levels of morbidity and death, especially in patients with renal involvement. Animal experiments have shown that ANCA directed against myeloperoxidase (MPO) can cause vasculitis that resembles human vasculitic disease (5,6); however, the cause of ANCA production remains unresolved.Theories have been developed to explain how ANCA could interact with neutrophils, along with monocytes and most probably T lymphocytes, to form the lesions that are characteristic of ANCA-associated vasculitis, such as fibrinoid necrosis and granulomas (7). A recent theory of interest has been postulated by Pendergraft et al. (8), stating that an antibody against the complementary peptide of proteinase-3 (PR3) in an idiotypic/anti-idiotypic network is essential to the development of ANCA and to the development of clinical vasculitis, but why and how these ANCA are produced in the first place remains unanswered. Nonetheless, many hypotheses have been developed about the initiating factor for ANCA production. Many factors, either directly or indirectly, have been considered important in the development of ANCA: Silica exposure (9); genetic predisposition (10); bacterial infection by Staphylococcus aureus (11); viral infection by, for instance, parvovirus B19 (12); and thyroid drugs (13) all have been correlated with and held to contribute to the incidence of ANCA-associated vasculitis. Some of these hypotheses are still th...

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Section: Silica and Vasculitismentioning

confidence: 97%

Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Wijngaarden¹,

Rijn²,

Hagen³

et al. 2008

Clinical Journal of the American Society of Nephrology

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“…Risk factors dor ESRD were serum creatinine at the time of the diagnosis, African American race and severity of histological lesions at biopsy [5]. The mortality in ESRD patients due to MPA was around 50% the prognosis was worse in patients with pulmorenal syndrome [33,34]. Death occurring during the first year of MPA immunosuppressive treatment was related primary to insufficient treatment response, several infections, cardiovascular disease and malignancy [4].…”

Section: Prognosismentioning

confidence: 99%

Microscopic Polyangiitis: from Pathogenesis to Treatment

Dousdampanis¹,

Assimakopoulos²,

Trigka³

2017

UNOAJ

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Microscopic Polyangiitis (MPA) is a systemic pauci-immune necrotizing vasculitis of small-calibre vessels characterized by the absence of granulomas. MPA is an autoimmune disease but its aetiology remains obscure. MPA is associated with presence of antineutrophil cytoplasmatic autoantibodies (ANCAs) but not all patients with MPA have ANCAs. There is strong evidence that not all ANCAs are pathogenetic. It seems that specific epitopes determine ANCAs pathogenicity. Given that MPA is a systemic vasculitis, multiple organs could be affected resulting in a wide spectrum of signs and symptoms. The kidneys and lungs are the most typical organs involved in MPA. Notably, MPA is the major cause of pulmo-renal syndrome. MPA has a poor prognosis if not treated but the use of aggressive immunosuppressive treatment has improved the prognosis and the patient's survival. Rituximab could be considered as an alternative treatment for severe disease, for patients who do not respond adequately to the immunosuppressive treatment and for patients with relapses. However, the long-term safety of Rituximab in MPA is unknown and it should be elucidated by further studies. Interestingly, kidney transplantation is safe and effective and it has a good prognosis in MPA patients with ESRD.

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“…4,5 Among the several types of systemic vasculitides that can present clinical manifestations of the pulmonary-renal syndrome, aside from Goodpasture's syndrome, are included: systemic lupus erythematosus, Henoch-Schonlein purpura, mixed cryoglobulinemia and more frequently, Wegener's granulomatosis and microscopic polyangiitis. 6 We focus the discussion on two types of vasculitides more often associated with antineutrophil cytoplasm antibodies (ANCA), microscopic polyangiitis and Wegener's granulomatosis, concerning a 10 year old girl with signs and symptoms of pulmonary-renal syndrome, with positive ANCA antimyeloperoxidase (anti-MPO) and rapidly progressive evolution.…”

Section: Introductionmentioning

confidence: 99%

“…The first pattern produces accentuated immunofluorescence in the central area of neutrophil cytoplasm (c-ANCA), and is constituted in its great majority by autoantibodies against the enzyme proteinase 3 of the azurophilic granules (anti-PR3); The other pattern, called perinuclear (p-ANCA), is frequently associated with autoantibodies against myeloperoxidase (anti-MPO), producing perinuclear or nuclear immunofluorescence. 6,14,15 The positivity of these autoantibodies is fundamental for the differential diagnosis of pulmonary-renal syndrome, firstly because it restricts that group of vasculitides practically to three entities: Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome, and also because they are highly sensitive and specific serological markers for those diseases, when serum is tested by indirect immunofluorescence combined with enzyme immunoassays for both PR3 and MPO. 5,12,13,16 The Churg-Strauss syndrome can be excluded from this discussion because, by definition, it demands the presence of asthma and eosinophilia, 10 which were not found in the described case.…”

Section: Introductionmentioning

confidence: 99%

“…4,17,18 The finding of antineutrophil cytoplasm antibodies in a patient with manifestations of pulmonary-renal syndrome is highly suggestive of the presence of microscopic polyangiitis or Wegener's granulomatosis. 6 The ANCA with cytoplasmic pattern (c-ANCA) and antigen specificity for proteinase 3 (anti-PR3) are very sensitive serological markers for Wegener's granulomatosis.…”

Section: Introductionmentioning

confidence: 99%

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Rapidly progressive antineutrophil cytoplasm antibodies associated with pulmonary-renal syndrome in a 10-year-old girl

Filho¹,

Ernesto²,

Rosa³

et al. 2001

Sao Paulo Med. J.

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CONTEXT: The term pulmonary-renal syndrome has been used frequently to describe the clinical manifestations of a great number of diseases in which pulmonary hemorrhage and glomerulonephritis coexist. The classic example of this type of vasculitis is Goodpasture´s syndrome, a term used to describe the association of pulmonary hemorrhage, glomerulonephritis and the presence of circulating antiglomerular basement membrane antibodies (anti-GBM). Among the several types of systemic vasculitides that can present clinical manifestations of the pulmonary-renal syndrome, we focus the discussion on two types more frequently associated with antineutrophil cytoplasm antibodies (ANCA), microscopic polyangiitis and Wegener´s granulomatosis, concerning a 10 year old girl with clinical signs and symptoms of pulmonary-renal syndrome, with positive ANCA and rapidly progressive evolution. CASE REPORT: We describe the case of a 10-year-old girl referred to our hospital for evaluation of profound anemia detected in a primary health center. Five days before entry she had experienced malaise, pallor and began to cough up blood-tinged sputum that was at first attributed to dental bleeding. She was admitted to the infirmary with hemoglobin = 4 mg/dL, hematocrit = 14%, platelets = 260,000, white blood cells = 8300, 74% segmented, 4% eosinophils, 19% lymphocytes and 3% monocytes. Radiographs of the chest revealed bilateral diffuse interstitial alveolar infiltrates. There was progressive worsening of cough and respiratory distress during the admission day, when she began to cough up large quantities of blood and hematuria was noted. There was rapid and progressive loss of renal function and massive lung hemorrhage. The antineutrophil cytoplasm antibody (ANCA) test with antigen specificity for myeloperoxidase (anti-MPO) was positive and the circulating anti-GBM showed an indeterminate result.

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The Syndrome of Lung Hemorrhage and Nephritis Is Usually an ANCA-Associated Condition

Cited by 175 publications

References 25 publications

Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Microscopic Polyangiitis: from Pathogenesis to Treatment

Rapidly progressive antineutrophil cytoplasm antibodies associated with pulmonary-renal syndrome in a 10-year-old girl

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