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71.
Lila Farrag William F. Pendergraft III J. J. Yang J. Charles Jennette Ronald J. Falk Gloria A. Preston 《Autoimmunity》2013,46(7):503-511
Proteinase 3 (PR3)-specific antineutrophil cytoplasmic autoantibodies (PR3-ANCA) recognize conformational epitopes on PR3. This study evaluates PR3-ANCA target epitopes utilizing a novel recombinant PR3 (rPR3) produced to accommodate manipulations of the N-terminal domain. The rPR3 molecule contains an N-terminus six histidine tag, which can be removed by enterokinase (EK) cleavage of an adjacent EK cleavage site. Once cleaved the remaining amino acids correspond to the mature N-terminus of PR3. This rPR3 can be manipulated to produce three variant forms: tagged rPR3+his, EK-cleaved (his-tag removed) rPR3? his, and EK-cleaved, denatured/refolded rPR3? his/dr (the proteolytically active form). Patients with clinically positive PR3-ANCA titers (n = 40) were confirmed for reactivity against purchased native PR3 in our system. Controls included 29 healthy volunteers and 34 MPO-ANCA patients. All PR3-ANCA sera samples tested were reactive with one or more forms of the recombinant protein (greater than mean ELISA OD 405 + 2 SDs of controls). Of significance, three sera were reactive with non-active forms only and three others were more reactive with rPR3? his/dr than with native PR3. The results of our evaluation of PR3-ANCA sera for reactivity against the three forms of our rPR3 protein uniquely exemplify the diverse array of epitopes within the PR3-ANCA population. This new recombinant form of PR3 should provide a suitable approach to mapping ANCA epitopes using site-directed mutagenesis. 相似文献
72.
Anna-Isabelle Kälsch Anthea Peters Birgit Buhl Annette Breedijk Katharina Prem Wilhelm H. Schmitt 《Autoimmunity》2013,46(5):467-474
It has been suggested that the retinoid X receptor beta (RXRB) gene is a risk factor for Wegener's granulomatosis. We addressed if there is a functional difference in the response to retinoic acid (RA) and vitamin D in Antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis (AASV) patients and if this was associated with RXRB genotypes. TNFα and IL-10 production were measured in whole blood assay from AASV patients (n = 51) and healthy controls (HC, n = 67). One micromolar of 1,25-(OH)2 D3, 9-cis RA (9c-RA) or all-trans RA (ATRA) was added to the assay. Genotyping was performed for exons 7 and 2 of the RXRB gene and for a microsatellite in vicinity of the RXRB gene. Lipopolysaccharide (LPS) mediated TNFα production and IL-10 were significantly lower in patients. Addition of 1,25-(OH)2 D3, ATRA or 9c-RA, blunted TNFα production, more pronounced in patients. Although all three compounds inhibited IL-10 production significantly in HC, only 1,25-(OH)2 D3 was found to be effective in patients. Allele distribution of the RXRB microsatellite differed significantly between patients and HC. This was not found for the SNP in exons 2 and 7. Genotype of the latter correlated with the ability of 1,25-(OH)2 D3 and ATRA to inhibit IL-10 production. We provide immunological evidence for a functional difference in vitamins D and A responsiveness in AASV patients. Since the inhibition of TNFα was more effective in patients, vitamin D supplementation might be an additional therapeutical approach. 相似文献
73.
74.
Natalya Maltseva Elena Borzova Daria Fomina Mojca Bizjak Dorothea Terhorst-Molawi Mitja Košnik Kanokvalai Kulthanan Raisa Meshkova Simon Francis Thomsen Marcus Maurer the COLD-CE Steering Committee 《Allergy》2021,76(4):1077-1094
Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU. 相似文献
75.
Panniculitides are a group of diseases characterized by an inflammatory process that originates primarily in the subcutaneous tissue. Histopathological classification of panniculitides in mostly septal or lobular types, according to the predominant localization of the infiltrate, is complemented with the eventual identification of vasculitis and the consideration of the vessel size. Additional steps involve the characterization of the inflammatory infiltrate and other findings, such as, the type of adipocyte necrosis or the presence of sclerosis, crystals and foreign bodies. Apart from this purely histopathological characteristics, clinico-pathological correlation is often required to encompass the clinical, histopathological and laboratory data in order obtain the correct diagnosis. We will review the classification of panniculitis, useful histopathological clues for their diagnosis and diagnostic algorithms that can be applied when sclerosis is present or the inflammatory infiltrate is mostly neutrophilic. 相似文献
76.
《Transfusion and apheresis science》2021,60(4):103157
IntroductionCutaneous leukocytoclastic vasculitis is an inflammatory variant of vasculitis with a variety of causes that only affects the skin. Its pathological manifestations include neutrophil infiltration and nuclear fragmentation. Clinically, it is characterised by a pleomorphic rash, including erythema, purpuric skin lesions, reticulocytosis, necrosis and ulceration. Once formed, local ulcerations are very difficult to heal.Case presentationA 46-year-old female was diagnosed with cutaneous leukocytoclastic vasculitis. The patient’s legs exhibited ulcers with a black eschar on the surface. The largest wound was 4.5 × 4.0 cm and the deepest wound was 1.7 × 1.8 × 1.0 cm. The ulcers had been present for 6 months and did not exhibit signs of healing. Treatment was commenced with platelet-rich plasma, and the wounds healed within 1 month.ConclusionTopical application of autologous platelet-rich plasma gel exerts beneficial effects in cutaneous leukocytoclastic vasculitis with regard to wound size reduction, and it induces granulation tissue formation. Platelet-rich plasma may represent a safe and cost-effective treatment for managing cutaneous wound healing to reduce the length of the recovery period. 相似文献
77.
Hania S. Zayed Amr Amin Samy Alsirafy Nahla D. Elsayed Soheir Abo Elfadl Mohamed Nasreldin Dalia Enaba Zeinab Nawito 《Arab Journal Of Gastroenterology》2018,19(2):71-75
Background and study aims
Central nervous system (CNS) involvement in hepatitis C virus (HCV) infection has different facets such as anxiety, depression, cognitive impairment and vasculitis. We were interested in detecting subclinical CNS involvement in chronic HCV infected subjects with and without systemic vasculitis.Patients and methods
Nineteen patients (15 females and 4 males) with chronic HCV infection (mean age 46.5?±?7 and mean duration since diagnosis of HCV infection 4.7?±?4?years, including 6 (32%) Child-Pugh class A cirrhotic patients) and 30 age, sex and education matched healthy control subjects were studied. Thirteen patients had associated vasculitis. Patients and control subjects were assessed using the block design and comprehension subtests of Wechsler Bellevue Adult Intelligence Scale, Wechsler Memory scale (WMS), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Brain HMPAO Single Photon Emission Computed Tomography (SPECT) was performed for HCV patients.Results
Patients with HCV had lower scores on the block design test compared to control subjects (8.37?±?1.89 versus 10.37?±?1.47, p?<?0.001), lower total WMS scores (43.15?±?10.49 versus 60.27?±?8.08, p?<?0.001) and higher anxiety and depression scores (16.94?±?10.46 and 37.17?±?10.38 versus 10.3?±?4.67 and 28.9?±?5.99, p?=?0.004 and 0.001, respectively). Total WMS were lower in HCV patients with vasculitis compared to those without vasculitis (39.14?±?9.3 versus 51.17?±?8.3, p?=?0.019) while the block design and comprehension tests, BAI and BDI were not significantly different between both groups. The block design and comprehension tests, WMS, BAI and BDI were not significantly different between cirrhotic and non-cirrhotic patients. Seven patients had different patterns of cerebral hypoperfusion on SPECT, and all of them had associated vasculitis. Abnormal SPECT was associated with lower total WMS scores (35.87?±?10.8 versus 46.79?±?8.6 in those with normal SPECT, p?=?0.049).Conclusions
Vasculitis may contribute to the development of neuropsychiatric involvement in HCV patients. 相似文献78.
Morelli S Gurgo Di Castelmenardo AM Conti F Sgreccia A Alessandri C Bernardo ML Valesini G 《Rheumatology international》2000,19(6):209-212
Wegener's granulomatosis (WG) is a systemic necrotizing vasculitis, which could potentially affect any organ system. However,
there have only been a few reports on cardiac involvement. We described the echocardiographic findings in nine patients affected
by WG. A complete M-mode, two-dimensional, Doppler and color-Doppler transthoracic echocardiogram was performed in nine patients
(seven females and two males) affected by WG. In each patient, cardiac abnormality, for example, valvular damage, left ventricular
global systolic dysfunction, or pericardial effusion, was detected. In particular, heart valve disease was found in eight
patients, and in three cases, aortic valve insufficiency, which was severe enough to require surgical valve replacement, was
observed. Cardiac involvement in patients with WG is common. In particular, there is a high frequency of aortic valve abnormalities.
Thus, an echocardiographic study should be routinely performed.
Received: 21 October 1999 / Accepted: 28 April 2000 相似文献
79.
Henoch-Schonlein purpura (HSP) is the most common acute vasculitis in the pediatric population, with an incidence of 10-14 per 100,000. The classic presentation of this disorder includes erythematous papules followed by palpable purpura in the lower extremities, trunk, and face, arthralgia or arthritis, abdominal pain, gastrointestinal bleeding, and nephritis. While renal abnormalities in HSP are common, the classic pulmonary manifestations, such as hemorrhage and pneumonitis, are thought to be infrequent. Subclinical pulmonary manifestations, including diffusion defects and radiographic anomalies, seem to be quite frequent in patients with HSP but are not commonly reported. Other respiratory manifestations include pleural effusion and chylothorax, but these are rarely mentioned in the literature. Chylothorax was only reported once in an adult patient with HSP in whom the mechanism of formation was demonstrated to be secondary to transdiaphragmatic passage of chylous fluid from the peritoneal cavity. Here we describe an 8-year-old girl with HSP, nephrotic syndrome, and chylothorax, and we report the results of a review of the literature regarding respiratory complications in HSP. The present case is the first pediatric patient reported with HSP and chylothorax. The therapeutic measures utilized were effective in resolving her edema, ascites, and chylothorax, and we advocate the use of these measures as first-line therapy in future patients with similar complications from HSP. 相似文献
80.