Twenty-five years of RENHIS: a history of histopathological studies within EUVAS.

In the early 1990s, an international working group of experienced renal pathologists, the Renal Histology group, set up a scoring system for biopsies with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis. This scoring system subdivided glomerular, interstitial and vascular lesions and served as a tool for the evaluation of all renal biopsies from studies of the European Vasculitis Study Group (EUVAS). Histopathological studies gave new insights into the prediction of renal outcome in patients with ANCA-associated glomerulonephritis. Percentage of normal glomeruli and a selected number of interstitial parameters were reliable predictors of long-term follow-up glomerular filtration rate in all studies. Out of these results, a histopathological classification distinguishing focal, crescentic, mixed and sclerotic classes of ANCA-associated glomerulonephritis was developed. Until today, 13 studies have validated this classification system. Future studies will try to determine if and how renal histology could be helpful in guiding treatment of ANCA-associated glomerulonephritis.

A historical essay on detection of anti-neutrophil cytoplasmic antibodies.

In this essay we describe a number of the known and not so known experiences of the early anti-neutrophil cytoplasmic antibodies (ANCAs) days, explaining why and how we reached consensus on the standard indirect immunofluorescence (IIF) techniques, the naming of the two principal C- and P-ANCA patterns, why we chose to use IIF as the standard technique, how the solid phase assays have developed and where we stand today, the use of ANCA for diagnosis and the importance of using several techniques for that purpose, how ANCA titres are related to disease activity and the clinical impact of this, and finally the implications of ANCA being a natural, polyclonal antibody response against various epitopes in relation to diagnostics and disease patterns.

The history of ANCA-associated vasculitis.

An essential early step toward understanding vasculitis was recognition in 1948 of the differences between the small artery disease of polyarteritis, essentially sparing the glomerulus and lungs, and disease of glomerular vessels and small veins, often involving the lungs. By 1951, Churg and Strauss drew on their knowledge of vasculitis literature and renal pathology to provide an authoritative description of the syndrome bearing their names. One year later a paper from Australia described a syndrome of febrile systemic illness with myalgias, arthralgias, microscopic hematuria, and a serum antibody reacting with neutrophil cytoplasm antigens. Within 30 years, nephrologists and immunologists in northern Europe linked antineutrophil cytoplasm antibodies to a specific vasculitis, Wegener's granulomatosis. Falk and Jennette later determined that pANCA reacted with cytoplasmic myeloperoxidase, and that cANCA did not; the antigen with which cANCA reacted was soon identified as a novel serine proteinase. New and better treatments of AAV will follow progress in understanding their pathogenesis.

Curso de reumatologia: aula 9: Anticorpo anticitoplasma de neutrófilos: significado clínico / Course of rheumatology: class 9: Antibodies antineutrophil cytoplasmic: clinical meaning

Os anticorpos anticitoplasma de neutrófilos são autoanticorps contra componentes neutrofílicos, úteis nos dianósticos diferenciais das vasculites. A imunofluorescência indireta determina três padrões de fluorescência: citoplasmático (cANCA), específico para granulomatose de Wegener; perinuclear (pANCA), observado na síndrome de Churg-Strauss, poliangiite microscópica e em outras vasculites; o terceiro padrão, atípico (aANCA), ocorre na doença de Crohn, colite ulcerativa e em outras doenças. O objetivo deste artigo é abordar os pontos importantes para a correta valorização dos achados da pesquisa de ANCAs, que possa auxiliar o clínico nos diagnósticos das síndromes vasculíticas. Os autores descutem a importância dos padrões de fluorescência, sua correlação antigênica e a possível significação clínica do ANCA positivo.

Antineutrophil cytoplasmatic antibodies (ANCA) are autoantibodies against components of neutrophils, and they help with the identification of different forms of vasculitis. The ANCA pattern, determined by indirect immunofluorescence, can be either cytoplasmatic (cANCA), which are predominantly associated sith Wegener's granulomatosis; or perinuclear (PANCA) are more likely seen in mocroscopic polyangiitis, Churg-Strauss syndrome and other vasculitides. The third pattern is atypical (aANCA) and it's reported in patients with ulcerative colitis, in patients with Crohn's disease and other illnesses. The present article seeks to make an approach on the most important points to be considered in the analyses and evaluation of ANCA test that might help the physician on diagnostic of vasculitis diseases. Authors discuss the importance of these immunofluorescence patterns, the antigen's correlation and the probably clinical significance of ANCA positive.

Antineutrophil cytoplasmic antibodies (ANCA).

Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80-90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10-20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10-20% of patients with WG or MPA (and 40-50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear. ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatment. A significant increase in ANCA titres, or the reappearance of ANCA, should alert the clinicians and lead to a stricter patient control.

Curso tópicos de medicina interna: aula 2: anticorpos anticitoplasma de neutrófilos (ANCA): significado clínico / Course topics of internal medicine: cClass 2: antineutrophil cytoplasmic antibodies (ANCA): clinical means

Os anticorpos anticitoplasma de neutrófilos (ANCA) são auto-anticorpos dirigigos contra as enzimas contidas nos grânulos dos neutrófilos e lisollomos de monócitos. Estão presentes em até 98 por cento dos casos de granulomatore de Wegener ativa, uma vasculite necrosante sistêmica, auxiliando no seu diagnóstico e seguimento pós-tratamento. Podem também ocorrer, com menor freqüência, nas glomerulonefrites pauci-imunes, nas poliangites microscópicas, nas doenças inflamatórias intestinais, nas colagenoses, em algumas neoplasias e doenças infecciosas. Podem ser detectados por imunofluorescência indireta (IFI), radioimunoensaio, ELISA e Western blotting. À IFI exibem dois padrões clássicos, o ANCA-C e o ANCA-P. Porém, outros padrões, diferentes dos clássicos podem ocorrer e são chamados ANCA-A ou atípicos. A grande dificuldade reside na interpretação destes testes e sua utilização na prática clínica. Assim, o objetivo deste trabalho é tornar o ANCA melhor conhecido pelos colegas não-familiarizados com o assunto e tentar esclarecer quando sua presença tem real significado clínico, evitando possíveis danos, por vezes irreversíveis, aos nossos pacientes.