Antineutrophil Cytoplasmic Antibody Specificity Research Articles

ANCA-associated renal vasculitis

The hemoglobin level was 8.8 g/dL with normal indices. The CASE PRESENTATION erythrocyte sedimentation rate was 70 mm/hr. C-reactive proA 62-year-old white woman presented to another hospital tein was 30 mg/L (normal 10 mg/L), and she had a positive with a five-week history of profound malaise and small joint antineutrophil cytoplasmic antibody (ANCA) test to a titer of arthralgia. Initially she had noticed a mild sore throat that set1:400 serum dilution by indirect immunofluorescence with a tled spontaneously. She had transient redness of her left conperinuclear pattern. Subsequent antigen-specific ELISA conjunctiva. One week after the onset of symptoms, she had a firmed reactivity to myeloperoxidase (MPO), denoting MPOsingle episode of macroscopic hematuria for which she received ANCA (Fig. 1). The ANA, anti-DNA, and anti-GBM antibody antibiotics from her family doctor. She denied dysuria or uritests were negative. Complement C3 and C4 levels were nornary frequency. For one week prior to admission, she had mal, and cryoglobulins were not detectable. Hepatitis B and suffered nausea and vomiting without abdominal pain or bowel C serologies were negative. After control of blood pressure, a disturbance. She had lost one stone (14 pounds) in weight. She renal biopsy was performed; the tissue contained eight glomerhad been hypertensive five years previously, but she had had uli. Of these, one was globally sclerosed, three were normal, no other antecedent illnesses. There was no family history of and four contained acute segmental lesions of various sizes renal disease, hypertension, or rheumatic complaints. She had with thrombosis, tuft disruption, and a few cells in Bowman’s four adult children, all of whom were well. Medication on space (Fig. 2). Tubules were acutely damaged, with blood in admission comprised a beta blocker (atenolol, 100 mg daily) a few. A patchy infiltrate of chronic inflammatory cells was for hypertension. She did not smoke cigarettes and drank less present. Small arteries and arterioles appeared virtually northan three units (24 g) of alcohol per week. She was a poultry mal. Immunoperoxidase study revealed no significant immunofarmer and lived in a rural setting. protein deposition within glomeruli. Clinical examination revealed that she was pale and dehyThe clinical history, renal biopsy findings, and blood serology drated. She had no rash, no active synovitis, and no lymphadewere consistent with an acute vasculitic (pauci-immune) glonopathy. Her temperature was 37.2 C; pulse, 70 beats/min; merulonephritis of the microscopic polyangiitis type. An assessand blood pressure, 160/90 mm Hg lying and 145/80 mm Hg ment of vasculitic activity showed a Birmingham Vasculitis Acstanding. Her jugular venous pressure was not elevated and she tivity Score (BVAS) of 13 and a Vasculitis Damage Index (VDI) had no sacral or ankle edema. The heart sounds were normal score of 0. Therapy with prednisolone, 1 mg/kg/day, and oral

Clinical value of antineutrophil cytoplasmic antibodies.

This article presents a brief review of the clinical value of antineutrophil cytoplasmic antibodies (ANCA) in the diagnosis and management of patients with various forms of vasculitis. ANCA assay methodology and testing recommendations are reviewed. The patterns of reactivity of ANCA observed by indirect immunofluorescence, the antigens recognized by ANCA, and the sensitivity, specificity, and positive predictive value of ANCA for diagnosis of different vasculitides are described. In addition, the spectrum of drugs and nonvasculitic diseases that are associated with ANCA and need to be differentiated from true ANCA-positive vasculitides are reviewed. When properly utilized and cautiously interpreted, ANCA are a useful, noninvasive diagnostic tool in the differential diagnosis of vasculitis.

Antineutrophil cytoplasmic antibodies (ANCA) and systemicvasculitis: update of assays, immunopathogenesis, controversies, and report of a novel de novo ANCA-associated vasculitis after kidney transplantation

Objectives: To characterize antineutrophil cytoplasmic antibodies (ANCA),their major autoantigens, disease associations, and pathophysiology in systemic vasculitides. To describe a patient with a novel de novo ANCA-associated vasculitis after kidney transplantation. Methods: We reviewed and compiled the literature on ANCA-related topicsand systemic vasculitis. Laboratory and clinical data from a cadaveric kidney transplant patient who developed necrotizing vasculitis involving glomerular capillaries, with crescent formation associated with P-ANCA and myeloperoxidase, were analyzed. Results: Large-scale multi-center testing of patient and normal sera by theEuropean ANCA Assay Standardization Project using immunofluorescence assays and enzyme immunoassays indicate the assays have good sensitivity and specificity, and diagnostic utility for ANCA-associated vasculitis. A few investigations covering basic and clinical research with ANCA remain controversial: whether endothelial cells do or do not express a 29-kd neutral serine protease termed proteinase-3 (PR-3), the target of ANCA in most individuals with Wegener's granulornatosis, and whether anti-myeloperoxidase (MPO) ANCAs recognize a restricted number of epitopes on MPO. This issue has relevance for using monoclonal antibodies to treat patients with vasculitis who have adverse effects from immunosuppressive drugs. The two allelic forms of FcγRlla (H131/R131) and the two of FcγRlllb (NA1/NA2) are discussed as possible inheritable genetic elements for vasculitic disorders and for signaling responses. Stimulatory and costimulatory molecules, and cytokine profiles of T lymphocytes are characterized to show that these cells are actively involved in the ANCA-associated vasculitides. The patient described had a de novo ANCA associated small vessel vasculitis which developed after renal transplantation. Conclusions: There have been significant advances in the development ofsensitive and specific ANCA assays. The immunopathogenetic mechanism of ANCA involves the constitutive FcγRs, ligands, and signaling responses to activate cytokine-primed neutrophils. This may lead to the generation of reactive oxygen intermediates, degranulation, and secretion of intracellular granule contents, and ultimately inflammation and vasculitis.

Polyarthrite, manifestation inaugurale d'une polyangéite microscopique. À propos de deux observations

Although joint manifestations are common in microscopic polyangiitis (MPA), including arthralgia reported in 15-65% of cases and arthritis in 6-17%, there have been only two published cases of polyarthritis as the first manifestation of the disease. We report on two new cases. A 71-year-old woman had symmetric polyarthritis of the hands which initially suggested the existence of seronegative rheumatoid arthritis. A 52-year-old woman had seropositive asymmetric oligoarthritis. The diagnosis was not established until renal insufficiency appeared, prompting a renal biopsy which showed in both cases an extra-capillary glomerulonephritis and an anti-myeloperoxydase (p-ANCA) assay which was postive in both patients. The incidence and specificity of antineutrophil cytoplasmic antibodies (ANCA), including MPA, in rheumatoid arthritis are reviewed. Our two observations show that in cases of polyarthritis or oligoarthritis with renal involvement, testing for and typing of ANCA should be performed so as not to misdiagnose vasculitis.

Anti-neutrophil cytoplasmic antibodies in a rat model of trinitrobenzenesulphonic acid-induced liver injury.

In sera from patients with autoimmune liver diseases, e. g. primary sclerosing cholangitis (PSC) and autoimmune hepatitis, anti-neutrophil cytoplasmic antibodies (ANCAs) can be found. Until now, no animal model of ANCA induction in liver disease has been described. In this study, we describe a novel rat model of acute liver injury and subsequent ANCA production. The hapten reagent 2,4,6-trinitrobenzenesulphonic acid (TNBS) was injected into the portal vein of female Lewis rats. Two experimental groups were studied: group A (TNBS/ethanol) received different TNBS concentrations; control animals of group B (ethanol) were injected with 10% (v/v) ethanol/0.9% (w/v) NaCl. A dose-dependent acute necrotizing liver injury occurred after injection of TNBS. Histopathological examination revealed acute hepatic injury with confluent parenchymal necrosis, mild bile duct proliferation and periportal infiltration. The periportal infiltration consisted mainly of macrophages and T lymphocytes. ANCAs were found in an allogenic test system between 1 and 8 weeks after TNBS injection in 11 out of 28 (39%) TNBS-treated rats (group A) and did not correlate with the extent of liver injury or TNBS dose. Autoantibody specificities of IgG type were directed against catalase (29%), myeloperoxidase (14%) and actin (7%), as detected by enzyme-linked immunosorbent assay and Western blotting. Moreover, autoantibodies against the asialoglycoprotein receptor were observed. Peripheral blood mononuclear cells and spleen lymphocytes from TNBS-treated rats were shown to produce ANCAs. In summary, we were able to show that intraportal administration of the hapten reagent TNBS induces an acute necrotizing liver injury with subsequent ANCA production in Lewis rats. ANCA specificities were mainly directed against catalase, an autoantigen that has recently been identified in sera from patients with primary sclerosing cholangitis and autoimmune hepatitis. This animal model offers the opportunity to study the pathomechanisms of ANCA production in necrotizing liver injury.

Churg-Strauss syndrome.

A syndrome comprising asthma, allergic rhinitis, pulmonary and systemic small-vessel vasculitis, and extravascular granulomas was described in 1951 by Churg & Strauss, mainly from autopsied cases (1). Clinical studies of patients with polyarteritis nodosa, associated asthma, pulmonary in®ltrates, and eosinophilia had been reported previously (2±5). Churg & Strauss described the pathologic lesions and distinguished this entity from polyarteritis nodosa. They described basic anatomic changes consisting of ``widespread vascular lesions of the type seen in polyarteritis nodosa, and of characteristic tissue alteration in the vessel wall and in the extravascular system. This tissue alteration . . . comprised necrosis of eosinophilic exudate, severe `®brinoid' collagen change, and granulomatous proliferation of epithelioid and giant cells.'' Churg & Strauss considered it to be a distinct histopathologic entity which they termed ``allergic granuloma''.

Antineutrophil cytoplasmic antibodies in children.

To define the diagnostic meaning of antineutrophil cytoplasmic antibodies (ANCA) positivity in children, we analysed 1485 consecutive sera sent for routine immunological investigation to our department from January to August 1996. Using this large screening, we identified the most typical clinical disorders associated with ANCA in childhood. Out of 1485 indirect immunofluorescence (IIF) tests for ANCA, 143 were ANCA positive, 70 had a cytoplasmic IIF pattern (c-ANCA), and 73 a perinuclear IIF pattern (p-ANCA). The ANCA associated diseases in childhood were cystic fibrosis (CF) (31 c-ANCA, 7 p-ANCA positive out of 71 CF children investigated), juvenile chronic arthritis (JCA) (21 p-ANCA positive out of 78), auto-immune hepatitis (AIH) (4 c-ANCA and 12 p-ANCA positive out of 19), and ulcerative colitis (UC) (2 c-ANCA, 5 p-ANCA positive out of 15). In cases of c-ANCA positivity we determined the antigenic specificity of ANCA for proteinase 3 and/or bactericidal/permeability increasing protein. Borderline anti-proteinase 3 levels were found in CF, and in high levels in one boy with Wegener granulomatosis. Bactericidal/permeability increasing protein was characteristic target antigen in children with CF. p-ANCA positive children were further tested for the specificity for myeloperoxidase, which was detected mostly in children with JCA. The spectrum of diseases associated with ANCA in children includes, besides the diagnostic associations typical for adults, several typical pediatric entities, mainly juvenile chronic arthritis and cystic fibrosis.

A panel set for epitope analysis of myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody MPO-ANCA using recombinant hexamer histidine-tagged MPO deletion mutants.

A major target protein of antineutrophil cytoplasmic antibody with a perinuclear staining pattern (P-ANCA) has been identified as myeloperoxidase (MPO). Recombinant deletion mutants of MPO, eight fragments of the heavy-chain subunit, and two fragments of the light chain subunit were expressed in E. coli using a pQE expression vector. The recombinant hexamer histidine-tagged fragments were partially purified as the denatured proteins on a Ni2+-charged nitrirotriacetic acid column. The recombinant fragments were reacted with a rabbit polyclonal antibody to human MPO in Western blotting. In addition, the reactivities of the proteins with MPO-ANCA-positive sera of four patients with renal diseases were examined by Western blotting. The profile of the reactivity showed that different sera recognized different sets of fragments of the heavy chain, whereas no serum reacted with the fragments of the light chain. These results indicate that the sera of patients with MPO-ANCA-positive diseases showed varied reactivities with the different fragments. Furthermore, an ELISA system using a set of the fragments completely purified by Sephacryl S-200HR column chromatography was established. The panel set is useful for subclassification of MPO-ANCA-related diseases.

Antineutrophil cytoplasmic antibodies in chronic liver diseases: prevalence, titre, specificity and IgG subclass

Background/Aims: Antineutrophil cytoplasmic antibodies are reported in patients with chronic liver disease, but controversy exists about their prevalence and specificity. We aimed to find the prevalence and specificity of antineutrophil cytoplasmic antibodies in chronic liver diseases by determination of antineutrophil cytoplasmic antibody titre and IgG subclass. Methods: One hundred and eight-four sera were studied: 63 primary sclerosing cholangitis, 28 autoimmune hepatitis, 34 primary biliary cirrhosis, 12 alcoholic liver disease, five large duct obstruction, four haemochromatosis, one chronic cholestatic syndrome, one cryptogenic cirrhosis and 36 normal individuals. Antineutrophil cytoplasmic antibodies were detected on alcohol-fixed neutrophils using an alkaline phosphates technique. The IgG subclass of antineutrophil cytoplasmic antibodies was determined using monoclonal antibodies: HP 6001 for IgG1, HP 6002 for IgG2, HP 6050 for IgG3 and SK 44 for IgG4 (Sigma Immunochemicals). Results: Antineutrophil cytoplasmic antibodies were detected in 65% of primary sclerosing cholangitis patients at a serum dilution of 1:5, dropping to 49% at 1:50. For autoimmune hepatitis, antineutrophil cytoplasmic antibodies were detected in 49% at 1:5, dropping to 11% at 1:50. Only 6% of primary biliary cirrhosis patients were antineutrophil cytoplasmic antibody-positive at 1:5, dropping to 3% at 1:50. All other controls were antineutrophil cytoplasmic antibody negative at 1:5. The presence of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis correlated with involvement of the intra- and extrahepatic biliary tree ( p=0.016, Fisher's exact test), but no other clinical parameters. Determination of the IgG subclass of antineutrophil cytoplasmic antibody in 33 primary sclerosing cholangitis and 11 autoimmune hepatitis patients revealed a predominance of IgG1 in both groups (94% and 82% of all IgG antineutrophil cytoplasmic antibodies, respectively), with a similar distribution of IgG2, IgG3 and IgG4 antineutrophil cytoplasmic antibodies between the groups. Conclusions: Antineutrophil cytoplasmic antibodies are specific to the autoimmune liver diseases, particularly primary sclerosing cholangitis and autoimmune hepatitis. Titres are highest in primary sclerosing cholangitis, with a diagnostic sensitivity of 49% and specificity of 89% at 1:50, making it a useful serological marker for this disease. The lack of correlation with any marker of activity and the association of antineutrophil cytoplasmic antibody with extent of biliary tract involvement suggest that antineutrophil cytoplasmic antibodies arises as a result of the disease or related process rather than being a cause of it. The detection of antineutrophil cytoplasmic antibodies in autoimmune hepatitis, together with a similar IgG subclass distribution of primary sclerosing cholangitis and autoimmune hepatitis antineutrophil cytoplasmic antibodies, may reflect similar mechanisms of immune regulation and a possible overlap syndrome. Future identification of the antigens against which this antineutrophil cytoplasmic antibody are directed should help to clarify this point, as well as allowing the development of a more sensitive and specific serological test for diagnostic purposes.

Anti-neutrophil cytoplasmic antibodies in childhood systemic lupus erythematosus

The prevalence and antigen specificity of anti-neutrophil cytoplasmic antibodies (ANCA) in sera from 23 children with active systemic lupus erythematosus (SLE) were studied utilizing indirect immunofluorescence and IgG and IgM ELISA using crude neutrophil extract and purified proteinase 3, myeloperoxidase, lactoferrin, cathepsin G and elastase. ANCA were present in 69% of SLE children and consisted of IgM and IgG antibodies of variable specificities, but did not correlate with organ involvement or disease activity. It remains unclear whether they have pathogenic significance or are epiphenomena in the category of polyclonal B-cell activation. However, their presence is entirely compatible with SLE even though they have hitherto been commonly associated with other systemic vasculitides.

Anti-neutrophil cytoplasmic antibodies in chronic inflammatory bowel disease. Prevalence and diagnostic role.

Anti-neutrophil cytoplasmic antibodies (ANCA), originally found to be associated with vasculitis, have been reported to be present in chronic inflammatory bowel disease. Most often the ANCA staining pattern is of the perinuclear type (p-ANCA), although nuclear and cytoplasmic stainings are seen. Single studies have shown some of the antibodies to react with lactoferrin or cathepsin G; however, most studies have not been able to determine a main antigenic specificity. We studied the prevalence of ANCA in sera from 155 patients with ulcerative colitis, 128 patients with Crohn's disease, and 51 patients with coeliac disease. The presence of ANCA was correlated to disease activity, extent, and age of onset of the diseases. Furthermore, we tried to characterize the antigen specificity by enzyme-linked immunosorbent assay (ELISA), using elastase, lactoferrin, myeloperoxidase, proteinase 3, and cathepsin G as antigens. The sera were screened for ANCA by indirect immunofluorescence. Anti-nuclear antibodies (ANA) were analysed on HEp2 cells, and ELISA for specific ANCA was performed using the antigens mentioned. Most of the sera with positive immunofluorescence had the p-ANCA type of pattern. Seventy-eight of 155 (50.3%) of the patients with ulcerative colitis were ANCA-positive, compared with 31 of 128 (24.2%) of patients with Crohn's disease (p < 0.001). However, in the subgroup with Crohn's colitis, 16 of 44 (36.4%) were ANCA-positive. Only 4 of 51 patients (7.7%) with coeliac disease showed positive immunofluorescence (p < 0.001 compared with ulcerative colitis). Less than 10% of the samples were positive in the specific ELISA assays; thus other than the most well known granule proteins can be the target for ANCA in ulcerative colitis. ANCA occur significantly more often in ulcerative colitis than in Crohn's disease. However, the prevalence of ANCA is rather high in Crohn's colitis. ANCA are thus of limited value in differentiating Crohn's colitis from ulcerative colitis. ANCA found in inflammatory bowel disease are different from those associated with vasculitis. The antigen(s) responsible remain to be determined.

Anti-neutrophil cytoplasmic antibody: a prognostic indicator in primary sclerosing cholangitis.

Considerable variability has been reported in the frequency and specificity of anti-neutrophil cytoplasmic antibody with a perinuclear staining pattern (pANCA) in patients with chronic liver disease, especially in primary sclerosing cholangitis (PSC), and in inflammatory bowel disease. This study examines the presence of pANCA in patients with these disorders, in particular those with PSC complicated by other biliary disease, and also patients who had undergone orthotopic liver transplantation. An indirect immunofluorescent technique was used to measure pANCA with serum diluted 1:20. Ten of 39 (26%) patients with PSC had detectable pANCA, as did two of nine (22%) with autoimmune chronic active hepatitis (AICAH) but none of the 51 patients with other forms of chronic liver disease. The presence of pANCA was significantly more frequent in patients who had PSC with biliary tract complications, in particular calculi (seven of 16 with vs three of 23 without; P = 0.03). Eight of the 12 pANCA-positive patients with PSC or AICAH had undergone hepatic transplantation. This was more likely than in patients with PSC or AICAH who were pANCA negative (10 of 36; P = 0.02). To date, pANCA has been detected after transplantation in four patients with PSC and one with AICAH. In patients with PSC or AICAH, pANCA should be sought as a marker of prognosis.

Diagnostic significance and antigen specificity of antineutrophil cytoplasmic antibodies in renal diseases. A prospective multicentre study. Italian Group of Renal Immunopathology.

In a prospective multicentre study on the clinical significance of ANCA in renal diseases, sera from 920 patients with rapidly progressive renal failure and/or renal disease in association with extrarenal signs suggestive of a systemic vasculitis were tested for the presence of ANCA by indirect immunofluorescence (IIF) and ELISA. 193 of 920 cases (20.9%) were positive by IIF and 180 (19.5%) by ELISA, using a 'crude' cytoplasmic extract as substrate. The sensitivity and specificity of IIF for 'pauci-immune' cresentic necrotizing GN (CNGN), in association or not with systemic vasculitis, was 87.5 and 95.6% respectively. The IIF pattern and antigen specificity (alpha granules and MPO) correlated well with the clinical features: a cANCA pattern (alpha granules) was associated with ENT involvement (probable Wegener's granulomatosis); a pANCA pattern (MPO) with 'idiopathic' CNGN and small-vessel vasculitis without respiratory tract disease (microscopic polyarteritis); patients with a pulmonary-renal syndrome had either c or pANCA in a similar proportion. Our study confirms a high sensitivity and specificity of ANCA for patients with CNGN. ANCA should be considered an important diagnostic test in patients with renal diseases, especially in the presence of rapidly progressive renal failure.

The value of indirect immunofluorescence and solid phase techniques for ANCA detection: A report on the first phase of an international cooperative study on the standardization of ANCA assays

This study describes the results of phase I of an international effort to develop and standardize assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). 12 sera, four of which were selected for their potential to cause problems in the detection of various ANCA specificities, were analyzed in the standard indirect immunofluorescence (IIF) test and in ELISAs for ANCA routinely performed in the seven participating laboratories. The IIF methodology differed with respect to the dilution of the serum being screened and the concentration of the conjugate used. Results from sera with high ANCA titers were similar, although the quantitative values could not be compared. In sera containing rheumatoid factor and anti-nuclear antibodies (ANA), ANCA-unrelated staining patterns were observed. Six antigen preparations were used in ELISA for the detection of cANCA. In ELISA with purified proteinase-3 all three cANCA sera were positive, but not anti-myeloperoxidase (MPO) or anti-lactoferrin (LF) positive sera. The other assays were less sensitive or gave inconsistent results. Various preparations of purified MPO and LF used in ELISA were readily recognized by anti-MPO and anti-LF positive sera. From this study it can be concluded that the IIF test, although performed with different methods, shows comparable results using strongly positive sera. In general solid phase assays for cANCA detection are not well standardized and need improvement although the purified proteinase-3 ELISA is possibly an exception. MPO and LF can be used in ELISA procedures for the detection of pANCA-related antibodies.

Clinical significance of ANCA in 98 patients.

Clinical and histological data leading to precise diagnosis were retrospectively obtained in 98 patients with antineutrophil cytoplasmic antibodies (ANCA) detected by indirect immunofluorescence (IIF). Specificity was determined by myeloperoxidase (MPO) and proteinase 3 (PR3) specific ELISA in all and a comparative study based on ANCA specificity was performed. Vasculitis was present in all cases. PR3-ANCA occurred predominantly in males (25/38) with WG (19/38). MPO-ANCA occurred predominantly in older women and were often associated with various autoimmune disorders. There was a high prevalence of lung hemorrhage (18/45) and mPA (26/45) in this group. Patients with negative MPO and PR3 specific ELISA despite positive IIF (n = 15) were almost exclusively WG (13/15) and were characterized by a high prevalence of hepatic and digestive manifestations. Renal and patient survival at the 75th percentile was 15 months with MPO-ANCA and 16 months with PR3, and was similar for patients with WG and mPA. With immunosuppressive treatment, ANCA disappeared in 66% of cases and this disappearance was always associated with absence of disease activity.

Antineutrophil cytoplasmic antibodies in IgA nephropathy and Henoch–Schönlein purpura

The frequency, isotype, and specificity of antineutrophil cytoplasmic antibodies were investigated in a cross-sectional study of 100 patients with IgA nephropathy and 30 children with Henoch-Schönlein purpura. Two of the patients with IgA nephropathy had high titres of antineutrophil cytoplasmic antibodies which were of IgG isotype and confirmed as antimyeloperoxidase antibodies in solid-phase ELISA and inhibition experiments. Antineutrophil cytoplasmic antibodies were not detected in the children with Henoch-Schönlein purpura and none of the patients in either group had IgA antineutrophil cytoplasmic antibodies. A further 20 IgA nephropathy and 10 Henoch-Schönlein purpura patients were studied longitudinally in different clinical phases at 4-monthly intervals over a 2-year period. None of these patients had or developed antineutrophil cytoplasmic antibodies. We conclude that IgA antineutrophil cytoplasmic antibodies are not involved in the vasculitis of Henoch-Schönlein purpura or in the pathogenesis of glomerular injury in IgA nephropathy. The detection of IgG antimyeloperoxidase antibodies in a small minority of IgA nephropathy patients extends the spectrum of diseases associated with autoimmunity to this antigen but is of uncertain significance.

Detection of antineutrophil cytoplasmic antibody in a patient with L-tryptophan induced eosinophilia-myalgia syndrome.

The Center for Disease Control has received numerous reports of an eosinophilia-myalgia syndrome related to products containing L-tryptophan. The case is reported of eosinophilia-myalgia syndrome and polyneuropathy associated with myeloperoxidase specific antineutrophil cytoplasmic antibody.

Antigen specificities and clinical distribution of ANCA in kidney diseases

The antigenic specificity and clinical distribution of the antineutrophil cytoplasmic antibodies (ANCA) in kidney diseases have recently been extensively studied. In patients with systemic vasculitis, the great predominance of two major ANCA antigens, proteinase 3 (PR3) and myeloperoxidase (MPO), is now established. PR3 and MPO are colocalized in the azurophilic granules of neutrophils and translocated to the cell surface during activation, and thus are able to interact with autoantibodies after neutrophil preactivation. Furthermore, by comparison of amino acid and DNA sequences, it has been shown that PR3 is identical to myeloblastin, which has been described independently and is involved in the control of growth and differentiation of leukemic cells. Aside from the two major ANCA antigens, a number of neutrophil cytoplasmic antigens recognized by ANCA have been identified, including human leukocyte elastase, lactoferrin, CAP57, and cathepsin G. These rare ANCA specificities occur in a limited number of patients. The variety of ANCA antigen specificities contrasts, however, with the fact that the vast majority of ANCA-positive sera are monospecific for one single ANCA antigen. With regard to clinical distribution, ANCA have major diagnostic significance in the four conditions in which they are frequently detected: Wegener's granulomatosis (WG), Churg and Strauss Syndrome (CSS), microscopic periarteritis (MPA), and necrotic and crescentic glomerulonephritis (NCGN). However, the initial dichotomy between MPO-associated vasculitis (NCGN, MPA) and that associated with anti-PR3 antibodies (WG) appears far from absolute.

Anti-neutrophil cytoplasmic antibodies in ulcerative colitis: Comparison with other colitides/ diarrheal illnesses

Previous studies from this laboratory showed that serum anti-neutrophil cytoplasmic antibodies, distinct from those associated with active Wegener's granulomatosis, are present in the majority of patients with ulcerative colitis. In this study, the specificity of anti-neutrophil cytoplasmic antibodies for ulcerative colitis as compared with other colitides and diarrheal illnesses was determined. In a blinded study, test samples of serum were screened for anti-neutrophil immunoglobulin G in a fixed neutrophil enzyme-linked immunosorbent assay. Levels of neutrophil binding by immunoglobulin G and titers of anti-neutrophil immunoglobulin G in sera from patients with ulcerative colitis and patients with ulcerative colitis post colectomy were each significantly greater than the levels and titers for normal controls and patients with a variety of other colitides and diarrheal illnesses. Levels of neutrophil binding for colonic Crohn's disease, bacterial/amoebic colitis, the irritable bowel syndrome with diarrhea, and other miscellaneous diarrheal illnesses were not significantly different than the levels for normal controls. Although the levels of binding for collagenous colitis were significantly less than the levels for ulcerative colitis, they were significantly greater than the levels for normal controls. Patterns of neutrophil binding by serum samples that were positive in the enzyme-linked immunosorbent assay were determined by indirect immunofluorescence. Perinuclear staining was the predominant pattern shown by sera from patients with ulcerative colitis. The combination of a positive value in the enzyme-linked immunosorbent assay and a perinuclear immunofluorescence pattern was 60% sensitive and 94% specific for ulcerative colitis. It is concluded that anti-neutrophil cytoplasmic antibodies in ulcerative colitis are not simply an epiphenomenon related to inflammation of the colon. Identification of the antigen(s) to which these autoantibodies are directed may facilitate understanding of the underlying immune response and may allow development of an assay that is more sensitive and specific for ulcerative colitis.

Anti-Neutrophil Cytoplasmic Antibodies in Ulcerative Colitis

Abstract Previous studies from this laboratory showed that serum anti-neutrophil cytoplasmic antibodies, distinct from those associated with active Wegener's granulomatosis, are present in the majority of patients with ulcerative colitis. In this study, the specificity of anti-neutrophil cytoplasmic antibodies for ulcerative colitis as compared with other colitides and diarrheal illnesses was determined. In a blinded study, test samples of serum were screened for anti-neutrophil immunoglobulin G in a fixed neutrophil enzyme-linked immunosorbent assay. Levels of neutrophil binding by immunoglobulin G and titers of anti-neutrophil immunoglobulin G in sera from patients with ulcerative colitis and patients with ulcerative colitis post colectomy were each significantly greater than the levels and titers for normal controls and patients with a variety of other colitides and diarrheal illnesses. Levels of neutrophil binding for colonic Crohn's disease, bacterial/amoebic colitis, the irritable bowel syndrome with diarrhea, and other miscellaneous diarrheal illnesses were not significantly different than the levels for normal controls. Although the levels of binding for collagenous colitis were significantly less than the levels for ulcerative colitis, they were significantly greater than the levels for normal controls. Patterns of neutrophil binding by serum samples that were positive in the enzyme-linked immunosorbent assay were determined by indirect immunofluorescence. Perinuclear staining was the predominant pattern shown by sera from patients with ulcerative colitis. The combination of a positive value in the enzyme-linked immunosorbent assay and a perinuclear immunofluorescence pattern was 60% sensitive and 94% specific for ulcerative colitis. It is concluded that anti-neutrophil cytoplasmic antibodies in ulcerative colitis are not simply an epiphenomenon related to inflammation of the colon. Identification of the antigen(s) to which these autoantibodies are directed may facilitate understanding of the underlying immune response and may allow development of an assay that is more sensitive and specific for ulcerative colitis.