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Cytoplasmic Autoantibodies (cytoplasmic + autoantibody)
Kinds of Cytoplasmic Autoantibodies Selected AbstractsA case of pulmonary arteritis with stenosis of the main pulmonary arteries with positive myeloperoxidase-antineutrophil cytoplasmic autoantibodiesRESPIROLOGY, Issue 4 2000Hiroyuki Nakayama A 53-year-old woman was referred to our hospital with the main symptoms of productive cough, fever and exertional dyspnoea. Chest X-ray revealed enlargement of the left hilar shadow and cavitary infiltration in the right upper lobe. 99mTechnetium-macroaggregated albumin (99mTc-MAA) perfusion scintigram showed complete hypoperfusion through the entire right lung. A pulmonary angiogram revealed stenotic lesions in the right and left main pulmonary arteries. Right cardiac catheterization showed an elevated right ventricular systolic pressure. There was no evidence of systemic arterial lesions nor vasculitis. The patient was positive for myeloperoxidase (MPO)antineutrophil cytoplasmic autoantibodies (ANCA) (168 EU). The Mycobacterium avium complex sputum culture was positive. The pulmonary stenotic lesions were surgically resected. The resected pulmonary arterial lesions were pathologically diagnosed as non-specific vasculitis. The cavitary lesion disappeared 6 months after the surgery. Two years after the surgery, although the MPO-ANCA level had decreased to 12 EU, stenosis of the pulmonary arteries reappeared. It is suggested that the patient became positive for MPO-ANCA in association with the Mycobacterium avium complex infection, and that the presence of MPO-ANCA may not be related to the development of pulmonary stenosis of the main pulmonary arteries. [source] ANCA-small vessel vasculitides: what have we (not yet) learned from animal models?APMIS, Issue 2009BETTY S. VAN DER VEEN Anti-neutrophil cytoplasmic autoantibodies (ANCA) with a specificity for myeloperoxidase or proteinase 3 are closely associated with small vessel vasculitides (SVV). In vitro, ANCA activate primed neutrophils to release toxic substances that destroy endothelial cells, suggesting a pathogenic role for these autoantibodies in disease development. However, to study the complex interplay between ANCA, neutrophils, and the local environment in vivo, animal models are required. Here, we will review the animal models developed for ANCA-SVV and discuss how these models have been applied to study ANCA-SVV pathogenesis. In addition, some directions for future research pertaining to unresolved issues relevant for the pathogenesis and immunogenesis of ANCA-SVV are proposed. [source] Coexpression of CD177 and membrane proteinase 3 on neutrophils in antineutrophil cytoplasmic autoantibody,associated systemic vasculitis: Anti,proteinase 3,mediated neutrophil activation is independent of the role of CD177-expressing neutrophilsARTHRITIS & RHEUMATISM, Issue 5 2009N. Hu Objective Wegener's granulomatosis (WG) is strongly associated with antineutrophil cytoplasmic autoantibodies (ANCAs) directed against proteinase 3 (PR3). Recent studies have shown that membrane-bound PR3 (mPR3) is differentially expressed and colocalizes with CD177/NB1 on circulating neutrophils. We undertook this study to assess the differential expression of CD177 on neutrophils from patients with ANCA-associated systemic vasculitis (ASV) in comparison with patients with systemic lupus erythematosus (SLE), patients with rheumatoid arthritis (RA), and healthy individuals, and to investigate whether colocalization of mPR3 and CD177 affects anti-PR3,mediated neutrophil activation. Methods Expression of CD177 and mPR3 was analyzed by flow cytometry on isolated neutrophils from patients with ASV (n = 53), those with SLE (n = 30), those with RA (n = 26), and healthy controls (n = 31). Neutrophil activation mediated by anti-PR3 antibodies was assessed by measuring the oxidative burst with a dihydrorhodamine assay. Results Percentages of CD177-expressing neutrophils were significantly higher in patients with ASV and those with SLE than in healthy controls. In 3 healthy donors, CD177 expression was not detected. After priming with tumor necrosis factor ,, neutrophils remained negative for CD177 while mPR3 expression was induced. Neutrophils from CD177-negative donors or CD177, neutrophils sorted from donors with bimodal expression were susceptible to anti-PR3,mediated oxidative burst. Variation in the extent of anti-PR3,mediated neutrophil activation among different donors occurred independent of the percentage of CD177-expressing neutrophils. Conclusion Membrane expression of CD177 on circulating neutrophils is increased in patients with ASV and in those with SLE, but not in RA patients. However, primed neutrophils from CD177-negative individuals also express mPR3 and are susceptible to anti-PR3,mediated oxidative burst, suggesting that recruitment of CD177-independent mPR3 is involved in anti-PR3,induced neutrophil activation. [source] Cerebral and Oculorhinal Manifestations of a Limited Form of Wegener's Granulomatosis With c-ANCA,Associated VasculitisJOURNAL OF NEUROIMAGING, Issue 1 2001Peterus Thajeb MD ABSTRACT The authors report on cerebral and oculorhinal manifestations in a patient with a cytoplasmic pattern of antineutrophil cytoplasmic autoantibody (c-ANCA),associated vasculitis. Recurrent Tolosa-Hunt syndrome, cavernous sinus syndrome, Raeder's paratrigeminal neuralgia, and seizures were the major clinical manifestations. Brain MRI showed localized enhancing lesions initially in the cavernous sinus and later in the convexity pachymeninges. The lesions disappeared following 9 months of oral prednisolone (15 mg/day) and cyclophosphamide (100 mg/day) therapy. The presence of c-ANCA, demonstration of vasculitis, and depositions of immunoglobulin G (IgG) and fibrinogen in the vessel walls of pachymeninges of the patient confirmed an immune-mediated cause of the vasculitis. Cranial pathology without renal and pulmonary involvement suggests a variant of Wegener's granulomatosis, which is called the "limited" form of Wegener's granulomatosis. [source] Granuloma formation in ANCA-associated vasculitidesAPMIS, Issue 2009PETER LAMPRECHT Granuloma formation is a key pathologic finding in two of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: Wegener's granulomatosis (WG) and Churg,Strauss syndrome (CSS). So far, no animal models have been established convincingly reproducing both vasculitic and granulomatous features typical of WG and CSS. In biopsies, granulomatous lesions are found both at distant extravascular sites and in the vicinity of inflamed vessels, e.g. in the lung. Intriguingly, WG-granulomata appear to display features of tertiary lymphoid tissue. Cartilaginous and osseous destruction is caused by granulomatous inflammation invading adjacent tissues. Rhinosinusitis is regularly encountered in WG and CSS. Septal perforation, saddle nose deformity, middle and inner ear symptoms, and granulomatous invasion of the palate, orbita, meninges, or the pituitary gland may complicate WG. Both common (e.g. FCGR3B copy number) and distinct (e.g. HLA-DP, IL-10.2) genetic factors have been identified in AAV potentially favouring inflammation and autoimmunity. The HLA-DPB1/RING1/RXRB region constitutes a quantitative trait locus for ANCA-positive WG with the strongest association to be reported up to now. A profound alteration of the T-cell response including Th1 and Th17 responses, anomalously NK-receptor-expressing ,NK-like' T cells, and dysfunctional regulatory T cells could facilitate and sustain granuloma formation and autoimmunity. [source] Coexpression of CD177 and membrane proteinase 3 on neutrophils in antineutrophil cytoplasmic autoantibody,associated systemic vasculitis: Anti,proteinase 3,mediated neutrophil activation is independent of the role of CD177-expressing neutrophilsARTHRITIS & RHEUMATISM, Issue 5 2009N. Hu Objective Wegener's granulomatosis (WG) is strongly associated with antineutrophil cytoplasmic autoantibodies (ANCAs) directed against proteinase 3 (PR3). Recent studies have shown that membrane-bound PR3 (mPR3) is differentially expressed and colocalizes with CD177/NB1 on circulating neutrophils. We undertook this study to assess the differential expression of CD177 on neutrophils from patients with ANCA-associated systemic vasculitis (ASV) in comparison with patients with systemic lupus erythematosus (SLE), patients with rheumatoid arthritis (RA), and healthy individuals, and to investigate whether colocalization of mPR3 and CD177 affects anti-PR3,mediated neutrophil activation. Methods Expression of CD177 and mPR3 was analyzed by flow cytometry on isolated neutrophils from patients with ASV (n = 53), those with SLE (n = 30), those with RA (n = 26), and healthy controls (n = 31). Neutrophil activation mediated by anti-PR3 antibodies was assessed by measuring the oxidative burst with a dihydrorhodamine assay. Results Percentages of CD177-expressing neutrophils were significantly higher in patients with ASV and those with SLE than in healthy controls. In 3 healthy donors, CD177 expression was not detected. After priming with tumor necrosis factor ,, neutrophils remained negative for CD177 while mPR3 expression was induced. Neutrophils from CD177-negative donors or CD177, neutrophils sorted from donors with bimodal expression were susceptible to anti-PR3,mediated oxidative burst. Variation in the extent of anti-PR3,mediated neutrophil activation among different donors occurred independent of the percentage of CD177-expressing neutrophils. Conclusion Membrane expression of CD177 on circulating neutrophils is increased in patients with ASV and in those with SLE, but not in RA patients. However, primed neutrophils from CD177-negative individuals also express mPR3 and are susceptible to anti-PR3,mediated oxidative burst, suggesting that recruitment of CD177-independent mPR3 is involved in anti-PR3,induced neutrophil activation. [source] Spatiotemporal expression of chemokines and chemokine receptors in experimental anti-myeloperoxidase antibody-mediated glomerulonephritisCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2009B. S. Van Der Veen Summary Myeloperoxidase (MPO)-anti-neutrophil cytoplasmic autoantibody (ANCA)-associated necrotizing crescentic glomerulonephritis (NCGN) is characterized by abundant leucocyte infiltration. Chemokines are chemotactic cytokines involved in receptor-mediated recruitment of leucocytes. Our objective was to analyse spatiotemporal gene expression of chemokines and chemokine receptors in anti-MPO-mediated NCGN, to find potential targets for intervening with leucocyte influx. NCGN was induced in mice by co-administration of anti-MPO immunoglobulin (Ig)G and lipopolysaccharide. mRNA expression levels of chemokines and chemokine receptors were analysed in whole kidney lysates as well as in laser microdissected glomeruli and tubulo-interstitial tissue 1 and 7 day(s) after NCGN induction. Several chemokines and chemokine receptors were induced or up-regulated in anti-MPO-mediated NCGN, both on day 1 (chemokines CCL3, 5; CXCL2, 5, 13; receptor CXCR2) and on day 7 (chemokines CCL2, 5, 7, 8, 17, 20; CXCL1, 2, 5, 10; CX3CL1; receptors CCR2, 8; CX3CR1). The expression levels of most chemokines and receptors were higher in glomeruli than in the tubulo-interstitium. Because of the temporal induction of CXCR2 on day 1, we hypothesized CXCR2 as a potential target for treatment in anti-MPO-induced NCGN. Inhibition of CXCR2 using a goat-anti-CXCR2 serum prior to NCGN induction increased glomerular neutrophil influx but did not affect crescent formation and albuminuria. In conclusion, expression levels of various chemokines and chemokine receptors were increased in anti-MPO NCGN, and expressed particularly in glomeruli. These chemokines and receptors may serve as potential targets for treatment. Inhibition of a single target, CXCR2, did not attenuate anti-MPO NCGN. Combinatorial interventions may be necessary to avoid redundancy. [source] | ||||||||||